Supported projects

What biomarkers for diagnosis and monitoring of treatment of GvHD?

The use of allogeneic hematopoietic cell transplantation (HCT) is the most potent immunotherapeutic treatment for hematologic diseases, but its practical use is impeded by acute and chronic graft-versus-host disease (GvHD). The diagnosis of GvHD relies almost entirely on clinical signs, and can only be confirmed by biopsy of target organs. Neither pre-transplant clinical characteristics nor transplant characteristics are reliably predictive of GvHD outcomes. Discovery and availability of biomarkers suitable for screening high risk patients using early, non-invasive, blood tests specific for GvHD-therapy resistance would significantly aid in the management of patients with this disease and would allow for rational drug development and drug approval by regulatory authorities. Using proteomics, it has been shown that plasma concentration of Suppression of Tumorigenicity 2 (ST2), accurately stratified patients according to risk of non-response to acute GvHD therapy in large retrospective sets. In recent experiments, we have also found that a four protein panel including ST2, CXCL9, MMP3 (matrix metaaloproteinase) and osteopontin is associated with the diagnosis of chronic GvHD. Based on our preliminary data, we propose to validate these biomarkers to predict response to aGvHD and cGvHD therapy and monitor response. The rationale for the proposed research is that when we are able to identify patients who are at particularly high risk for unresponsiveness to standard treatment and subsequent mortality, we can porpose customized treatment plans. We plan to use a well-established ELISA workflow biomarkers on aGvHD and cGvHD samples. ST2, Reg3α, TNFR1, IL-6 will be validated on 300 matched aGvHD patient samples pre-treatment and 1month post-treatment. The pre-treatment samples will allow assessing of their predictive values. We will then create an informative and clinically useful biomarker panel to the prediction of responsiveness to therapy using a statistical approach to integrate the information gathered for the biomarkers in this aim. Regarding cGvHD, the candidate biomarkers are ST2, CXCL9, MMP3 and OPN. We will validate this predictive panel on 300 matched cGvHD patients samples pre-treatment and 3 months post-treatment. The same statistical approach as for aGvHD will be used. We anticipate that these aims will yield the following expected outcomes : First, validating multilayer biomarker panel that predicts response to aGvHD and cGvHD therapy in a European multicenter cohort. Second, we will determine the threshold of the different biomarkers that will provide the best sensitivity for future use in clinical trials. These outcomes are expected to have a major impact, because the panels of biomarkers are likely to be applied in future GvHD therapeutic trials as surrogate marker for clinical response, and the biomarkers have potential as GvHD-specific therapeutic targets.

Project leaders
Dr Etienne Daguindau (Hematology Department, CHRU Besançon), and Pr Pierre‐Simon Rohrlich (Pediatric Hematology-Oncology Unit, Archet Hospital, CHU Nice)
Academic PI members of CRYOSTEM consortium

Key figures
Call for project  2014
Project duration: 2 years
Number of patients involved: 227
Total number of samples: 500 (Plasma)

Project status : complete

Publications : NA

Are other atypical white blood cells an asset to address complications?

The mucosa-associated invariant T (MAIT) cells are innate-like T cells with restricted T cell receptor (TCR) usage, which are preferentially localized in mucosal tissues (liver, lung and gut) and respond to microbial infection by rapidly producing cytokines and cytotoxic effectors. They recognize the non-classical MHC-related molecule MR1, which binds an presents a novel class of antigens, namely precursor derivatives of vitamin B2 (riboflavin), which are found in most bacteria and yeasts. Upon bacterial stimulation, MAIT cells display immediate effector activity, namely production of pro-inflammatory cytokines (TNFα, IFNγ, IL-17) and cytotoxicity. In certain circumstances, MAIT cells are also able to produce IL-22, a cytokine involved in gut epithelial protection during inflammatory intestinal damage. Given the potential importance of MAIT cells in control of microbial infections and protection of epithelial surfaces, we investigated MAIT cell reconstitution in 43 children who underwent hematopoietic stem cell transplantation (HSCT) after myeloablative conditioning for the treatment of malignant hematological disease. MAIT cell numbers remained very low during the first 12 months after HSCT in recipients of matched-related or unrelated donor, and were almost undetectable in cord blood recipients. However, large interindividual variability was observed, suggesting that peritransplant factors might influence MAIT cell recovery. Furthermore, no export of naïve (thymic) MAIT cells was observed during the 12 months follow-up. We want to rapidly confirm and extend these preliminary results. The CRYOSTEM collection offers us a unique opportunity to obtain rapid results, in order to: 1/ confirm the kinetics of MAIT cell recovery and maturation over the first year after HSCT in matched-related donor recipients with myeloablative conditioning; 2/ determine if early MAIT cell recovery, and export of naïve MAIT cells from the thymus, are improved in matched-related donor recipients with reduced intensity conditioning compared to those with myeloablative conditioning; 3/ to determine if an early and efficient MAIT cell recovery is associated with clinical outcomes, in particular acute GVHD or bacterial infections. Given our strong expertise in MAIT cell analysis, the proposed research should be completed within 6 months, and should lead to a comprehensive assessment of the role of MAIT cells in HSCT recipients.

Project leaders
Pr Jean-Hugues DALLE (Pediatric Hematology-Oncology Unit, Robert Debré Hospital AP-HP) and Pr Sophie CAILLAT-ZUCMAN (Center of Research on Inflammation, Inserm, CNRS, Paris Diderot University)
Academic PI members of CRYOSTEM consortium

Key figures
Call for project 2014
Project duration: 1 year
Number of patients involved: 55
Total number of samples: 468 (Cells in DMSO)

Project status : complete

Publication :
TOURRET M ET AL., 2021 
Human MAIT cells are devoid of alloreactive potential: prompting their use as universal cells for adoptive immune therapy. Journal for ImmunoTherapy of Cancer.

 A new class of immune cells to predict GvHD?

Recently, a non-T cell lymphoid population was identified as another source of cytokines, the Innate Lymphoid Cells. These cells represent new effectors in the establishment of the mucosal immune response. In close contact with the epithelial cells of respiratory and intestinal mucosa, they are first in line to respond quickly to any disruption of the environment. Our team contributed to the discovery of these new lymphocyte populations in humans. ILCs can be categorized as cytotoxic ILCs, represented by NK cells, and helper-like ILCs, represented by the ILC1, ILC2 nd ILC3 subsets. The ILC3 produce IL-17 and/or IL-22. They are important in the epithelial regeneration and mucosal immunity by their secretion of antimicrobial peptides. By restoring hematopoietis, hematopoiteic stem cells (HSC) transplantation is the reference treatment of severe, non-malignant and malignant blood diseases. For the latter, it allows the patient to benefit from the maximum anti-leukemic conditioning « dose effect » (HD chemotherapy and total body irradiation) and the anti-leukemic immunological effect of the graft on minor antigens (mHAgs) expressing- leukemic cells («Graft versus Leukemia » effect). But preparing regimens (conditioning) can cause serious harm to mucosal tissues by inducing apoptosis of rapidly dividing epithelial cells. Moreover, the immunological effect exposes the patient to graft against the mHAgs of host cells, leading to graft versus host disease (GvHD). GvHD and immune deficiency inherent to the kinetics of reconstitution are two major immunological complications of HSC transplantation, and represent the main cause of mortality and post-transplant morbidity. A recent report from Hanash et al. Showed that the type 3 cytokine IL-22 mediates a protective effect on immune-mediated tissue damage occuring after bone marrow trannsplant in the mice. The source of IL-22 was shown to be ILC. This prompted researchers to investigate ILC in patients receiving HSCT. It was recently shown the apparition of activated NCR+ ILC3, not present in healthy persons, after conditioning regimen and allogeneic HSCT in a very small cohort of 6 patients. Interestingly these cells also expressed homing receptors to skin and gut which are the main sites of GvHD. Their data suggest that ILC recovery affects the development of GvHD. We propose to determine whether the appearance of distinct ILC subsets in peripheral blood, particularly the activated NCR+ ILC3, and the cytokine secretion signature of these subsets can be associated with clinical events post-graft such as GvHD. At our knwoledge, it is the first study studying the contribution to GvHD of peripheral blood ILC subsets in a large cohort of adult and pediatric patients. Currently there is no way to efficiently predict the occurrence of GvHD after HSC transplantation. If it is confirmed that the appearance of an ILC subset post-conditioning can be associated with a reduced risk of GvHD, this will lead to modulate preventive treatment in patients with a high risk of GvHD. Indeed, these ILC subsets could be good candidates for autologous cell therapy approach after in vitro expansion.

Project leader
Dr Frédéric Vély (Immunology Department – Hôpital de la Conception, Marseille)
Academic PI non-member of CRYOSTEM consortium

Key figures
Call for project 2014
Project duration: 1 year
Number of patients involved: 124
Total number of samples: 1 056 (Cells in DMSO)

Project status : complete

Publication :
PIPEROGLOU C, LARID G, VALLENTIN B, ET AL., 2021
Innate lymphoid cell recovery and occurrence of GvHD after hematopoietic stem cell transplantation. J Leukoc Biol. 2021;1–12.

The occurrence of EBV-associated PTLDs is generally preceded by an increase in viral reactivation- related viral EBV load and an increase in the number of infected B cells. Regular monitoring of the EBV viral load by PCR in the whole blood or plasma of allograft patients is therefore currently recommended to allow for pre-emptive therapy based on immunosupressive modulation and / Use of a monoclonal anti-CD20 antibody targeting B lymphocytes (Rituximab). This measure of viral load in the blood is not standardized and lacks both sensitivity and specificity, which leads to too late diagnoses of PTLD or to Unnecessary treatment. Other virological or immunological biomarkers are necessary to complete the measurement of the EBV blood viral load and to improve its predictive value. Recent results from our laboratory showed that this protein could be “excreted” and detected simply by an enzyme immunoassay in serum of transplant patients suffering from PTLD. For the first time we succeeded to detect the soluble ZEBRA (s-ZEBRA) protein in serum from transplant patients (measured by an antibody-based ELISA). The s-ZEBRA (>100 ng/mL) was predictive in 80% PTLD-patients within ten weeks, prior the PTLD diagnosis (p<0,0001) (Retrospective clinical study with 66 transplant patients. We hypothesize that early EBV replication may occur in the tumor or its environment, and eventually release of the ZEBRA in the bloodstream. At the end, this phenomenon could lead to the secretion of cytokines and factors promoting angiogenesis, B-cell proliferation, and thereby further aggravating the immunosuppressive environment.

The objective of this project is to confirm the clinical utility of this new biomarker (s-ZEBRA) as a surrogate of the EBV load measured by qPCR in a larger retrospective follow up study (HSC transplant patients). The ultimate goal will be to (i) predict not only malignant lymphoproliferation but also pejorative events in such patients (PTLD, GvHD, severe viral syndromes), (ii) define the first warning signal to reduce the dose of immunosuppressive drugs (the rituximab depletes B cells harbouring the latent EBV). Methods: 11 HSC transplant patients with PTLD and 40 GHVD patients were selected from the Cryostem database, in addition to 15 other HSC transplant patients from University Medical Center (Utrecht, NL). 45 solid organ transplant patients have been selected from other database in France (CIC Thorax, collection of CHU Strasbourg, DIVAT collection CHU Nantes) and will be investigated in parallel. From these collections, the serum samples will be tested for the soluble ZEBRA protein. Briefly an antigen-capture ELISA method was developed specifically for measuring sZEBRA in serum samples, using two specific monoclonal antibodies. A standard curve was obtained based on serial dilutions of r-ZEBRA, ranging from 1ng/mL to 250ng/mL. The results were expressed as concentrations of ZEBRA (ng/mL) extrapolated from the standard curve. In view of determining the detection specificity, three positive serum samples were submitted to a neutralization test.

Expected results: The test will be a new approach in monitoring EBV-related pathologies and adapting immunosuppressive therapy to transplantation. In addition, this new test can be used in the therapeutic follow-up of PTLD management, allowing individual evaluation of treatment efficacy, as well as in the development of new anticipated therapeutic approaches. Early detection will make it possible to adapt the doses of immunosuppressive drugs and / or to initiate an anti-CD20 treatment targeting the tumor cells.

Project leader
Pr Emmanuel Drouet (Joseph Fourier University  – Grenoble 1)
Academic PI non-member of CRYOSTEM consortium

Key figures
Call for project 2017
Project duration: 18 months
Number of patients involved: 61
Total number of samples: 132 (Plasma)

Project status : complete

Publication :

LUPO J. ET AL., 2022

High Predictive Value of the Soluble ZEBRA Antigen (Epstein-Barr Virus Trans-Activator Zta) in Transplant Patients with PTLD. Pathogens 2022, 11(8), 928

Death following acute GVHD is the major cause of non-relapse mortality after allogeneic stem cell transplantation (alloSCT). Our previous reports provided evidence that this complication is associated with endothelial cell dysfunction that can either be demonstrated at onset of acute GVHD or even be predicted prior to conditioning therapy for alloSCT. Predictive endothelial associated markers included angiopoietin-2, serum nitrates, suppressor of tumorigenicity (ST)-2 and SNPs in the thrombomodulin gene. The close relation of transplant-associated microangiopathy (TAM) and death of acute GVHD led us to construct the Endothelial Activation and Stress Index (EASIX): ‘LDH(U/l) x creatinine (mg(dl) / thrombocytes (/nl)’. This simple formula was validated in 3 independent cohorts and predicts death after acute GVHD at disease onset and prior to alloSCT (manuscript submitted). However, TAM associates with only half of the deaths from acute high grade GVHD, and patients with low EASIX scores still have a considerable risk of dying from this condition. Our search for this alternative pathomechanism now led to the proposal of a dysfunctional CXCR3 axis as the potential cause of death. CXCR3 is a chemokine receptor expressed on activated T lymphocytes, in particular on Th1 cells, NK cells, dendritic cells, and subsets of epithelial and endothelial cells. Here we have studied if a dysfunctional CXCR3 axis might be involved in GVHD pathogenesis and could link endothelial and T cell pathology in acute GVHD.

We assessed concentrations of the CXCR ligands CXCL9, CXCL10 and CXCL11 as well as anti-CXCR3 autoantibodies in 119 patients with high grade (3-4) acute intestinal GVHD for whom serum was available at GVHD onset. Furthermore, anti-CXCR3 autoantibodies and CXCL9 levels were measured in sera stored before conditioning therapy. All variables were tested for influence on post-GVHD survival using cause-specific Cox regression analysis.

At GVHD onset, high serum levels of CXCL9/MIG and a high EASIX score were strongest predictors of NRM. In patients with low EASIX, high CXCL9/MIG and low anti-CXCR3 serum levels independently predicted outcome in multivariable analyses. A score based on CXCL9, anti-CXCR3, and EASIX allowed an effective prediction of acute GVHD outcome ranging from mortality >90% (high CXCL9 + high EASIX) to mortality <20% (low CXCL9, low EASIX, high anti-CXCR3.

Our data suggest a strong role for the CXCR3 axis in the pathology of acute high grade GVHD that complements the established pathomechanism of endothelial cell dysfunction. The opposing effects of CXCL9 and anti-CXCR3 indicate a functional, attenuating role for these auto-antibodies. The overall prognostic impact of the immune-modulating CXCR3 axis appears to depend on the underlying integrity of the patients’ endothelial homeostasis.

Project leader
Dr Thomas Luft  (Department of Internal Medicine V: Hematology, Oncology and Rheumatology – University Hospital Heidelberg)
Academic PI non-member of CRYOSTEM consortium
Country : Germany

Key figures
Call for project 2017
Project duration: 6 months
Number of patients involved: 136
Total number of samples: 136 (Plasma)

Project status : complete

Publication : NA

Unmanipulated haplo-identical transplantations combining Cyclophosphamide in high doses with the immunosuppressive agent, mycophenolate have now proved their efficacy. They appear to have similar results to geno-identical transplantation in terms of overall survival, NRM and acute GVH. However, although NRM is low, early viral infections have been reported by different teams, either with CMV reactivation or with polyomavirus infections. Recent data have suggested that the HLA-G and HLA-E molecules have both humoral and cellular anti-inflammatory and immunosuppressive properties. HLA-G and HLA-E polymorphisms have been shown associated with various chronic viral infections including human immunodeficiency virus, papillomavirus, cytomegalovirus (CMV) and hepatitis viruses. Several recent studies have suggested that HLA-E and HLA-G polymorphisms were correlated with the occurrence of HSCT patients. Our Preliminary data on cohort of 108 patients with haplo-identical transplantation showed that the polymorphism HLA-E*01:03 homozygous in donor or recipient were associated with occurrence to chronic GVH.

Thus, the objective of this study is to determine the clinical relevance of the HLA-G / HLA-E genetic status of the donor / recipient pair in haplo-identical transplantations without T-depletion with cyclophosphamide at J3-J4.

This is a 7-month retrospective study of adult patients receiving haplo-identical transplants whose clinical data and at least one dry pellet of the donor / recipient couples are available at the CRYOSTEM Biological Resource Center . In practice, this study will take place in the EFS HLA laboratory and the “Blood Group Biology” department led by Dr. Christophe Picard, according to the following points: i) To extract of the DNAs from the dry pellets and aliquot. ii/ To Perform HLA classical, HLA-G and HLA-E as well as the HLA-G regulatory regions typing in the donors / recipients by two NGS techniques detecting the polymorphisms on all genes, one developed within the team of “Blood Group Biology” and one commercial (NGS-Go, EFS) iii / To determine in silico HLA-G/-E alleles and haplotypes-G iv / To determine impact of HLA-G and/or HLA-E polymorphisms and haplotype-G in the donor and recipient and their compatibility on NRM, viral infection, overall survival, relapse-free survival, acute disease and chronic graft against the host.

This study may help to introduce additional criteria into the donor selection algorithm and also to propose a different therapeutic strategy according to the non-classical HLA status for patients who have received a haplo-identical transplant.

Project leader
Dr Christophe Picard  (UMR 7268 ADÈS Aix Marseille University / EFS/ CNRS Marseille)
Academic PI member of CRYOSTEM consortium

Key figures
Call for project 2017
Project duration: 7 months
Number of patients involved: 330
Total number of samples: 660  (Dried white blood cell pellets)

Project status : complete

Publication : NA

Despite new drugs, allogeneic hematopoietic stem cells transplantation (HSCT) is frequently indicated in different hematologic disorders. The mean goal is to obtain allogeneic effect by donor immunologic system. If this effect is clearly demonstrated, some hematological malignancies appear less susceptible, in particular in lymphoid malignancies as non-Hodgkin’s large B-cell lymphomas (DLBCL) and Hodgkin lymphomas. The differences between these diseases are not clearly explained finally. Immune tolerance as described in the carcinogenesis mechanisms is potentially considered.

PD-1 (Programmed Death 1)(CD279) is an inhibitor receptor who attenuate the signal of the TCR(T-cell Receptor). With his ligand, PD-L1, they have a role to inhibit immune response and induce immune tolerance. Aberrant expression in hematologic disorders can inhibit T-cells in the tumor microenvironment and participate for the development of the tumor. This model is described in different pathologies as Hodgkin disease.

In otherwise, PD-1/PD-L1 could have a role for immunomodulation after allogeneic HSCT. It could be participated to inhibit Graft Versus Host Disease (GvHD) and anti-tumor effect, principal goal of HSCT. Currently, no data are described in vivo.

The aim of our study is to investigate the expression of PD-1 expression on the T-cells and plasma level of PD-L1 during allogeneic HSC transplants for the treatment of hematological malignancies and to determine whether there is an association between expression and prognosis after transplant HSC. Of the final goal is to define how use or not in some patients anti-PD1 therapy.

Project leader
Dr Jérome Cornillon  (Clinical hematology department, Institut de Cancérologie Lucien Neuwirth, University Hospital Saint Etienne)
Academic PI member of CRYOSTEM consortium

Key figures
Call for project 2017
Project duration: 1 year
Number of patients involved: 60
Total number of samples: 540  (Viable cells in DMSO, blood plasma)

Project status : complete

Publication : NA

Allogeneic hematopoietic stem cell transplantation (HSCT) is a major curative treatment for hematologic malignancies, and for inherited or acquired hematopoiesis disorders. However, it is still hampered by a high mortality rate. Graft-versus-Host Disease (GVHD) is a frequent and severe complication of allogeneic hematopoietic stem cell transplantation (HSCT).

Much of our knowledge on the pathophysiology of GVHD has been gained from experimental animal models. Recent advances in basic biology open new avenues to the development of biomarker sets that could predict GVHD severity and prognosis, and that could be tested and validated through well-designed multicenter clinical trials. However, it is still challenging to determine to what extend data obtained from biomarkers could be translated in terms of pathophysiology of alloimmune response.

The main goal of this project is to further our understanding of the pathogenic mechanisms of human GVHD on one hand, and of functional immune tolerance on the other. To this end, we will analyze metabolomics, transcriptomics and phenotypic data obtained from the analysis of donor’s immune system and from recipients at different periods after HSCT. We aim to identify biological and immunological variations between donor’s immune system at steady state, and those of patients with or without acute GVHD early after HSCT, and in long-term survivors without GVHD nor immunosuppressive drugs. This global and integrated approach will help to identify main pathways involved in acute GVHD and in tolerance mechanisms in humans.

We propose a retrospective analysis of a cohort of 130 patients transplanted from an HLA-identical sibling donor. Analyses will be performed during 2 critical, clinically relevant, periods. Period 1: Analysis at the onset of acute or 90 days after HSCT in patients not developing GVHD. Period 2: In “tolerant” patients (more than 1 years after HSCT and not requiring immunosuppressive treatment), or in patients still requiring immunosuppressive therapy after 1 year. We will use mass cytometry (CyTOF technology) to deeply phenotype donors and recipients lymphocytes subsets. Data will be analyze using dimensional reduction analysis (viSNE) and semi-supervised learning algorithms such as SPADE or CITRUS to design predictive and correlative mathematical models in order to identify cellular subsets involved in acute GVHD, chronic GVHD and tolerance induction after allo-HSCT. We will complete this approach with transcriptomics analysis based on NanoString technology and metabolomics analysis of patients plasma. Preliminary data were obtained from a cohort of 55 patients transplanted at Saint- Louis hospital. We were able to identify new lymphocytes subsets predictive of acute GVHD in recipients and donors. Tolerance induction is currently under investigation using a similar approach. We will confirm and extend these data to a larger multicenter national cohort obtained from the Cryostem.

Perspectives: The longitudinal design of this study will allow us to provide an integrated view of GVHD pathophysiology and mechanisms of immune tolerance in human. Identification of cellular, transcriptomics or metabolomics profile associated with GVHD or tolerance in donors and/or recipients may provide new tools predictive of transplant outcome.

Project leader
Dr David Michonneau (Service d’hématologie Hôpital Saint-Louis, Paris)
Academic PI member of CRYOSTEM consortium

Key figures
Call for project 2017
Project duration: 2 years
Number of patients involved: 130
Total number of samples: 1965  (Viable cells in DMSO, blood plasma)

Project status : complete

Publications :

DUBOUCHET L. ET AL., 2022 Operational tolerance after hematopoietic stem cell transplantation is characterized by distinct transcriptional, phenotypic, and metabolic signatures. Science Translational Medicine. 2022. 14 (633). DOI: 10.1126/scitranslmed.abg3083
LATIS E. ET AL., 2020 Cellular and molecular profiling of T-cell subsets at the onset of human acute GVHD. Blood Advances. 2020. 4 (16): 3927–3942. doi.org/10.1182/bloodadvances.2019001032
MICHONNEAU D. ET AL., 2019 Metabolomics analysis of human acute graft-versus-host disease reveals changes in host and microbiota-derived metabolites. Nature Communications. 2019 Dec 13;10(1):5695. doi: 10.1038/s41467-019-13498-3.

Allogeneic hematopoietic stem cell (HSC) transplantation (allo-HSCT) is complicated in 30 to 50% of the cases by Graft Versus Host Disease (GVHD), in which donor’s immunocompetent cells recognize and attack host’ tissues by similar allo-reactivity mechanisms than those inducing the GvL effect. The development of acute and chronic GVHD in allo-HSCT performed with an HLA-geno-identical donor suggests the involvement of antigens / peptides, recognized by donor T lymphocytes, presented by recipient’s HLA molecules but derived from genes encoded outside of the HLA system. Actually, immunocompetent donor cells can recognize the recipient’s immunopeptidome, which corresponds to all the peptides presented by individual’s HLA molecules. This peptidome is derived from proteins encoded by genes located throughout the genome and not only from the genes encoding HLA molecules. When the peptide presented by recipient’s cells is not part of the immunopeptidome of the donor, the immunocompetent cells of the donor can develop an immune reaction against this antigen.

Objectives : Determine whether the difference in the immunopeptidome between geno-identical donor and recipient predicts the occurrence of acute and chronic GVHD after allogeneic HSCT.

We will determine the degree of immunopeptidome incompatibility between donor and recipient (D/R) outside the HLA locus by sequencing the exomes (coding regions) of the D / R couple genes. We will determine an allogeneic mismatch score between donor and recipient (alloscore or allogenomics mismatch score, AMS). This score depends on the number and type of mismatches between proteins expressed by the donor (or recipient) and not known by the recipient (or donor) (D / R genomic incompatibility score for a given D / R pair). In order to limit biases related to other clinical factors potentially involved in the occurrence of GVHD and relapse, the study will be carried out in a homogeneous cohort of patients. We chose to analyze 15 donor / recipient pairs not developing acute or chronic GVHD, 15 pairs developing only acute GVHD and 15 pairs developing only chronic GVHD after allo-HSCT.

In a second part, we will determine in silico (via NetMHCPan tool) the peptides derived from the donor and the recipient presented with high affinity (IC50 < 500 nM) by their HLA class I and II molecules. The percentage of peptides presented specifically by the recipient will correspond to a second genetic incompatibility score in the GVH sense. We then will study whether the expression of these recipient’s peptides is correlated to the clinical expression of acute or chronic GVHD (recipient organs).

Perspectives : We hypothesize that acute and/or chronic GVHD could be predicted by the level of immunopeptidome incompatibility between donor and recipient. These data could thus improve the prevention and management of this disease and the choice of the best donor. Moreover, this first study could allow us to determine the potential interest of these alloscores in the prediction of the risk of relapse. These data would need to be confirmed on a second validation cohort.

Project leaders

Pr Marie-Thérèse Rubio and Dr Alice Aarnink (Service hématologie du CHU de Nancy – Hopitaux de Brabois)
Academic PI members of CRYOSTEM consortium

Key figures
Call for project 2017
Project duration: 3 years
Number of patients involved: 50
Total number of samples: 150  (Dried white blood cell pellets)

Project funded by the Association Laurette Fugain and Vaincre la Leucémie

Project status : complete

Publication :

DHUYSER A. et AL.,  Comparison of NK alloreactivity prediction models based on KIR-MHC interactions in hematopoietic stem cell transplantation. Frontiers in Immunology. 2023 Mar 2;14. doi: 10.3389/fimmu.2023.1028162

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a major treatment for hematopoietic malignancies, whose efficacy is mainly due to anti-tumoral response induced by donor T cells (graft versus leukemia effect). Graft-versus-host disease (GVHD) occurs when donor T cells recognize and target healthy tissues in recipients. Recently, a double-blind, randomized multicentre clinical trial (ALLOZITHRO) evaluated the effect of azithromycin (AZM) on airflow decline-free survival after allo-HSCT. It was prematurely discontinued due to an increased incidence of relapse in the AZM arm (HR 1.7 [1.2 – 2.4], P = .002), without any impact on GVHD incidence.
The aim of the present project is to understand mechanisms underlying relapses in patients treated with AZM. Three main hypotheses could explain the increased incidence of relapse in these patients: (1) a direct immunosuppressive effect of AZM (2) an inhibition of anti-tumoral response due to gut microbiota modifications and (3) a direct effect of AZM on tumor cells.
We have all blood and feces samples collected before and after transplantation for patients included in the ALLOZITHRO clinical trial. In patients treated with AZM or placebo, we will determine: (1) deep phenotype of circulating immune cells (2) gut microbiota characteristics, (3) plasma, cells and feces metabolomes. We will evaluate immune and microbiological status of patients, and existing relationship between microbiota and immune system. Finally, we will study AZM effect on tumor cell using an ex vivo co-culture assay.

Project leaders

Pr Anne Bergeron and Dr David Michonneau, Saint-Louis Hospital, Paris, AP-HP
Academic PI members of CRYOSTEM consortium

Key figures
Call for project 2018
Project duration: 2 years
Number of patients involved: 240
Total number of samples: 1 714  (Dried pellets, viable cells in DMSO and plasma)

Project status : complete

Publications :

VALLET N. ET AL., 2022

Azithromycin promotes relapse by disrupting immune and metabolic networks after allogeneic stem cell transplantation. Blood

VALLET N. et AL., 2023

Circulating T cell profiles associate with enterotype signatures underlying hematological malignancy relapses. Cell Host & Microbe.

Several studies have shown that the presence of antibodies in the recipient before graft and directed against the incompatible antigens of the donor called DSA (donor specific antibody) may induce graft failure or delayed engraftment in haplo-identical transplantations (HIT).
Due to frequent anti-HLA immunization in a family, the donors may also be immunized against the incompatible antigens of the recipient. This kind of antibodies is called RSA for recipient specific antibodies.
So far, no publication has studied the impact of the RSA on HIT.
The purpose of the project is to look for RSA in the pre-graft plasmas of the donors and to evaluate their impact on the outcome of the HIT, it means on acute or chronic Graft-versus-Host Disease (GVHD), relapse, survival and graft failure.
The RSA search will be done by LabscreenTM mixed for the screening followed in case of positivity by LabscreenTM Single antigen (OneLambda) in order to determine the specificity and the affinity of the antibodies. The antibody affinity is estimated through the MFI (Median Intensity Fluorescence). The comparison of the recipient’s HLA typing with the specificities of the donor’s antibodies will be used to assess the presence or absence of RSA.
After the determination of the presence of RSA in all the HIT of the cohort, the group of HIT with RSA will be compared to that without RSA for the occurrence of acute or chronic GVHD, relapse, graft failure and survival. The impact of the level of the MFI will also be tested.
We expect from this study to determine if the RSA are deleterious or not for the HIT and in case of deleterious effect, the importance of the level of MFI.
These answers will allow a rational management of the donors for HIT.

Project leaders
Dr Kahina Amokrane, laboratoire d’immunologie et Histocompatibilité, Hôpital Saint-Louis, Paris
Academic PI members of CRYOSTEM consortium

Key figures
Call for project 2019
Project duration: 1 an
Number of patients involved: 412
Total number of samples: 412  (plasma)

Project status : experiments in progress

Publication : NA

Hematopoietic stem cell transplantation is a treatment intended for some blood cancers and other blood diseases indicated in approximately 2,100 people in France and approximately 10,000 people in Europe and the United States each year. Although this treatment enables to cure patients from their initial pathology, some transplanted patients develop severe, and sometimes fatal, complications, such as when the donor’s blood cells attack the recipient’s tissues or organs, leading to multiple damage. This complication, known as the Graft-versus- Host Disease or GvHD, occurs in approximately 50% of patients receiving a blood cell transplantation. However, there are a limited number of approved therapies for the treatment of GvHD, and many patients do not respond to first-line steroid therapy. In addition, patients who answer steroids often need these drugs in large doses and for a long time, increasing the risk of major side effects. It is also important to note that when a patient develops GvHD, there is no test that can predict which drug will work for them. Rheos Medicines has identified an enzyme that may be involved in blood cells responsible for GvHD. A new treatment targeting this enzyme is currently under development. Samples from patients included in the CRYOSTEM cohort could be used to test whether this new treatment can suppress the activity of blood cells that cause GvHD, an important step in demonstrating the effectiveness of this new treatment. Historically, GvHD has been recognized as a difficult complication to treat due to its unpredictable development – multiple organs can be affected in different people – and the disease can progress more or less quickly. Therefore, in parallel with the development of a new treatment, the aim is to identify patients with GvHD who will be most likely to respond to this treatment. Using state-of-the-art laboratory and computational biology methods, the effect of several types of molecules on cells responsible for the progression of GvHD will be evaluated in order to identify “molecular signatures” that will increase chances of developing an effective new treatment for GvHD.

Project leader
Dr Joanna DiSpirito, Rheos Medicines
Biotechnology company based in the United States

Key figures
Access to the collection : 2020
Project duration: 1 year – Pilot study authorized by CRYOSTEM Scientific Committee
Number of patients involved: 68
Total number of samples: 694 (Plasma and cells)

Project status : complete

Publication : NA

Sobi study aims at evaluating the Interferon Gamma (IFNγ) signature in patients with different forms of Graft-versus-Host Disease (GvHD). The objective of the study is in particular to understand the relationship of the levels of Interferon Gamma and the activity of Interferon Gamma present in the blood with different forms of graft versus host disease, the cutaneous, digestive, hepatic and pulmonary forms as well as their severity.

Project leader
Dr Emmanuel Monnet, Sobi
Swiss biotech company

Key figures
Access to the collection : 2020
Project duration: 1 year – Pilot study authorized by CRYOSTEM Scientific Committee
Number of patients involved: 52
Total number of samples: 52 (Plasma)

Project status : complete

Publication : NA

As part of the understanding of the acute form of graft versus host disease, Genentech approached CRYOSTEM to analyze samples from the CRYOSTEM cohort. The research of this project will focus on an analysis of biomarkers. This research phase aims to understand the impact of these biomarkers in order to develop a screening and/or efficacy measurement device for the treatment of patients suffering from graft-versus-host disease in its acute form. . This project requires a panel of patient samples meeting certain very specific clinical criteria.

Project leader
Dr Annemarie Lekkerkerker, Genentech

Biotechnologies company

Country : USA

Key figures
Access to the collection : 2020
Project duration: 6 months

Total number of patients : 10

Total number of samples: 20 (Plasma)

Project status : complete

Publication : NA

Acute graft versus host disease (aGVHD) still represents a significant source of morbidity and mortality after allogeneic hematopoietic cell transplantation (allo-HCT) and may be associated with a dismal prognosis, especially in case of steroid-refractoriness.Its pathophysiology is dominated by the reaction of the donor-derived cellular immune system against multiple, so far undescribed recipient antigens on the surface of healthy tissues. This feature has been shown to be associated with the hyper-expansion in peripheral blood and targeted tissues of few T-cell populations with selective antigen-recognition specificity, well assessed in allo-HCT studies exploiting high throughput T-cell receptor (TCR) clonotyping or spectratyping. Similar mechanisms of clonal dominance have been described in other immune-related and lymphoproliferative disorders such as idiopathic aplastic anemia (IAA) and large granular lymphocyte leukemia (LGLL), whereby this lymphoid clonality can be associated with somatic genetic aberrations involving genes able to constitutively activate lymphocyte proliferation (i.e., JAK1, STAT3, STAT1, etc.).We hypothesize that such genomic alterations, and the aberrant derived signals, may play a role in defining the T-cell clonality also in an aGVHD scenario, possibly explaining specific steroid-refractory patterns.

Project leader
Dr Simona Pagliuca, Cleveland Clinic Foundation, Ohio, USA and CHRU Nancy, Service d’Hématologie, Nancy

Academic PI member of CRYOSTEM consortium

Key figures
Access to the collection : 2021
Project duration: 1 year
Number of patients involved: Selection on going
Total number of samples: Selection on going

Project status : feasibilty study completed. Selection of the biological resources for further study on going

Publication : NA

BK virus hemorragic cystitis (BKVHC) is a frequent complication following allogenic hematopoietic stem cell transplantation (allo-HCT), with incidence rates ranging from 11 to 22%. Despite the identification of several clinical risk factors for BKVHC (such as HLA mismatch, cord blood units, myeloablative conditioning regimen), BKVHC still results in significant morbidity, and has also been associated with impaired long-term kidney function. Previous studies have shown conflicting results regarding the link between pre-transplant recipient BKV serology, and post-transplant BK viruria or viremia. Moreover, the impact of the donor BKV serology, or pre-transplant BKV T-cell response have not been evaluated. Finally, leucocytes have been showed to harbor latent BKV, raising the possibility of BKV transmission through the donor during allo-HCT.

The primary objective of this study is to determine if there is an association between pre-transplant donor and/or recipient BKV immunological status and the occurrence of BKVHC following allo-HCT. The secondary objective is to determine if there is an association between BKV DNA detection in donor leucocytes and the occurrence of BKVHC in recipient.

Project leader
Dr Julien Gras, Infectious Diseases Department, St Louis Hospital, AP-HP, Paris

Academic PI member of CRYOSTEM consortium

Key figures
Access to the collection : 2021
Project duration: 1 year
Number of patients involved: 28
Total number of samples: 272

Project status : experimental studies in progress

Publication : NA

Pathogenic T-cell responses in T cell-mediated diseases, such as graft versus host disease (GvHD) and acquired aplastic anemia, can be driven by cytokines of the common gamma chain (γc) cytokine family (IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21). Collectively, these six cytokines play crucial roles in the development, proliferation, survival, migration, and effector functions of multiple immune cell populations, most notably T lymphocytes and natural killer (NK) cells. Each of the γc cytokines signals through a common receptor subunit, interleukin 2 receptor subunit gamma (IL2RG).

To understand the therapeutic potential of blocking γc cytokine-driven immune pathology, Regeneron generated REGN7257, a fully human IL2RG monoclonal antibody that inhibits signaling of all γc cytokines. Preclinical data demonstrated the ability of REGN7257 to suppress pathogenic T-cell responses through in vitro functional assays as well as mouse models of T cell-mediated disease, including models of graft-versus-host disease (GvHD) and immune aplastic anemia.

To better understand the role of γc cytokine signaling in human disease, Regeneron seeks to collaborate with CRYOSTEM and leverage CRYOSTEM’s prospective biobank of human blood samples derived from allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients and relevant matched controls. Pre-transplant biospecimens from subjects with aplastic anemia and longitudinal samples from allo-HSCT recipients who developed acute and/or chronic GvHD, will be analysed against matched controls to evaluate i) cellular expression patterns of γc cytokine family receptor subunits, ii) immune cell phenotypes and response to γc cytokines, and iii) changes in γc cytokine levels, soluble receptors, immune cell populations, and proteomics over time.

Perspectives: Together these analyses will inform our understanding of the role of γc cytokines in acquired aplastic anemia and GvHD pathogenesis, and thus the potential role of IL2RG blockade with REGN7257 in the treatment of these diseases.

Project leader
Dr Kerry Casey, Precision Medicine, Regeneron Pharmaceuticals Inc.

Biotechnologies company

Country : USA

Key figures
Access to the collection : 2022
Project duration: 1 year
Number of patients involved: 40
Total number of samples: 437

Project status : samples provision in progress

Publication : NA

Acute myeloid leukemia (AML) is a hematological malignancy and has a poor prognosis.
Despites recent advances in understanding its molecular landscape, the only curative option remains allogeneic hematopoietic stem cell transplantation. Targeted therapies developed in the last decade are only effective for certain subgroups of patients, and immunotherapies have so far shown disappointing results. Additionally, CAR and other adopted T cell therapies have been hindered by a lack of AML-specific neoantigens. Therefore, identifying such molecular targets is crucial for improving the outcomes of these therapies. Recent research by our group and others has shown that alternative splicing events may occur in cancer and may be a source of tumor-specific neoantigens. We have also shown that lung cancer patients are able to develop specific T cells response against alternative splicing-derived peptides. We have also demonstrated that lung cancer patients can develop specific T cell responses against alternative splicing-derived peptides. We have developed a pipeline to identify cancer-specific peptides using RNAseq and immunopeptidomics public and in-house data. We applied this pipeline to AML data and identified 8 candidate peptides, which correspond to 12 peptide-MHC molecule (pMHC) combinations.

Our goal is to search for specific T cell responses directed against these pMHC combinations in samples of patients with AML in complete remission. We will use pre-transplant samples from the CRYOSTEM collection, and matched sibling donors will be used as controls. Patients will be selected based on their HLA typing to match pMHC combinations. After thawing, half of each sample will be used directly, and the other half will be cultured with IL-2 and the appropriate peptides to select and expand specific T cells. Biotinylated MHC class I monomers (easyMers®) will be loaded with candidate peptides and tetramerized using streptavidin coupled with a fluorochrome. Tetramers and samples from patients and their donors will be incubated together and analyzed by flow cytometry. Identifying T cell specific responses in patients will open multiple possibilities in the fields of vaccination, TCR-like antibodies, and TCR-based cell therapies.

Project leader
Dr Aurélien Sutra del Galy, U932 Immunity and Cancer, Team Amgorena, Institut Curie

Academic not member of CRYOSTEM network

Key figures
Access to the collection : 2023
Project duration: 1 year
Number of patients involved: Selection in progress
Total number of samples: Selection in progress

Project status : samples selection in progress

Publication : NA

Due to advances in the detection and treatment of cancers, we have seen profound improvements in childhood cancer survival (84.1%, all cancers), and this can be largely attributed to the use of aggressive, multi-modal cancer treatments. However, these treatments come with the cost of increased prevalence and severity of long-term side-effects.
Haematopoietic stem cell transplant (HSCT) is often used to treat blood malignancies, but many transplant recipients develop graft vs. host disease (GvHD), a life-threatening side-effect of the donated cells reacting against recipient body tissues. Chronic and debilitating cognitive impairment is a common side-effect of GvHD, the pathogenesis of which is largely unknown.
However, what is known is that the GvHD significantly depletes beneficial microbes within the gut microbiota and in doing so reduces levels of microbial metabolites (SCFAs) which promote brain function and strengthen the protective blood-brain barrier. As such, we hypothesise that SCFA supplementation will strengthen the blood-brain barrier and this augmented protection will work to lessen the damage to the central nervous system sustained during GvHD.

To investigate this hypothesis we will analyse plasma from children who have undergone HSCT +/- GvHD using mass spectrometry for SCFA levels and ELISAs for biomarkers of blood-brain barrier damage and brain function. In parallel we will treat our blood-brain barrier
on-a-chip with these plasma samples and determine the effect of GvHD plasma upon barrier integrity. This barrier on-a-chip is a 3D cell culture of human stem cell derived endothelial cells forming microvessels which are perfused to replicate blood-flow, and are co cultured with neurons and astrocytes to represent the brain. This blood-brain barrier model will then be supplemented with exogenous SCFAs (butyrate, propionate and acetate) to determine the efficacy of microbial metabolites to prevent GvHD-induced barrier leakage.

This project is clinically relevant with gut microbiota-based therapies already in use in a number of clinical trials for cancer treatment side-effects, with established safety and efficacy. As such, evidence from this project indicating the effectiveness of SCFAs to alleviate central nervous system damage via reinforcing the blood-brain barrier will be streamlined for clinical translation. Particularly, given that the blood-brain barrier on-a-chip utilises paediatric stem cells, we are ensuring our results are age-matched for paediatric survivorship cohorts. Currently, for children who develop GvHD following stem cell transplant there are no therapies which incorporate preserving neurological function. The outcomes of this study endeavour to address this lack, by strengthening the innate protective mechanisms of the brain

Project leader
Dr Hannah Wardill, Supportive Oncology Research Group, University of Adelaïde

Country : Australia

Academic not member of CRYOSTEM network

Key figures
Access to the collection : 2023
Project duration: 1 year
Number of patients involved: Selection in progress
Total number of samples: Selection in progress

Project status : samples selection in progress

Publication : NA

When a cancer develops and progresses in a patient, it means that the adaptive immune system of this patient is not successful or no longer able to control and eradicate the tumor cells. The latter are however recognizable as foreign by the immune system, in particular by the T lymphocytes, of the patient. T lymphocytes are major players in this adaptive immune system, since they are able to recognize and eliminate pathogens, but also cells that have undergone a malignant transformation. In recent years, anti-tumor immunotherapy strategies have been developed and clinically evaluated. Their goal is to restore the ability of T cells to recognize and eliminate tumor cells from a cancer patient. Among these anti-tumor immunotherapy strategies, those involving CAR-T cells have made it possible to obtain spectacular remissions in patients with hematological malignancies. A CAR-T cell is produced from the patient’s T lymphocytes, taken from a blood sample. These T lymphocytes are cultured in vitro for about ten days, in order to be expanded, and they are genetically modified in order to be able to specifically recognize tumor cells in order to then eliminate them. These cultured and genetically modified lymphocytes constitute the batch of CAR-T, which will be reinjected into the patient from whom they are derived.

Despite the success encountered clinically in the treatment of hematological malignancies, relapses remain frequent and the strategy is struggling to be extended to the treatment of solid tumours. There are many ways to improve the CAR-T production process; among these, some make it possible to specifically target the expansion phase in vitro, which has the characteristic of causing accelerated aging of T lymphocytes and therefore making them less capable of persisting in the long term in the patient. We propose, in our study, to improve the quality of CAR-Ts cultured in vitro by causing an imbalance in the use of the different metabolic pathways that they have at their disposal, to favor the use of oxidative phosphorylation to the detriment of one involving aerobic glycolysis. Indeed, the implementation of oxidative phosphorylation is an indicator of less aging in the T lymphocyte, unlike that of aerobic glycolysis, associated with early differentiation. To do this, we chose to target the phenomenon of competition between different cellular enzymes for access to the metabolic cofactor NAD+. The need for NAD+ from certain glycolysis enzymes pushes the cell to regenerate it during the aerobic glycolysis mechanism, to the detriment of oxidative phosphorylation. The CD38 protein is another cellular enzyme that consumes a lot of NAD+ and its expression is particularly high in activated T lymphocytes. Our objective, in this project, is to inactivate the gene encoding CD38 using the Crispr/Cas9 molecular scissors technique, and thus to restore an appropriate balance between aerobic glycolysis and oxidative phosphorylation within the CAR-T and therefore to limit its in vitro aging during its expansion phase. After validating this hypothesis, we will characterize the phenotype and function of the CAR-Ts thus produced, as well as their ability to persist and infiltrate the target tissue in vivo.

Project leader
Dr Patricia Letondal and Pr Yann Godet, UMR 1098 RIGHT INSERM, EFS Franche-Comté

Academic member of CRYOSTEM network

Key figures
Access to the collection : 2023
Project duration: 18 months
Number of patients involved: Selection in progress
Total number of samples: Selection in progress

Project status : samples selection in progress

Publication : NA

Telomerase is an enzyme that plays a crucial role in maintaining the length of telomeres, which are protective structures at the ends of chromosomes. It’s activity is dedicated to decrease over time, leading to senescence and programmed cell death. In certain circumstances, cells can activate telomerase thus preventing their telomere shortening and allowing for continued cell division which is a characteristic feature of cancer cells.
The overexpression or upregulation of telomerase in acute myeloid leukemia (AML) can be attributed to several factors, including genetic mutations, alterations in the expression of telomerase components, and changes in the regulation of telomerase activity. Mutations in genes such as TERT (telomerase reverse transcriptase) and TERC (telomerase RNA component) can directly impact telomerase function and contribute to the development and progression of AML. Targeting telomerase has emerged as a potential therapeutic strategy for cancers. Our group has identified peptides derived from TERT (called UCP for “Universal Cancer Peptide”) that are able to stimulate CD4 T-cells Th1 (Godet et al, Clin Can Res 2012). This specific T-cell response has been associated with favorable outcome in solid cancer patients (Laheurte et al, Oncoimmunology 2016).Thus, we developed an UCP-based vaccine in patient with refractory advanced lung cancer that has been shown to be safe, highly immunogenic and associated with interesting OS.

Our goal is to provide insights in the specific T cell response directed against TERT (CD4 anti-TERT) in the context of allogeneic hematopoietic transplantation (alloSCT) for AML. To do so, we will address those questions :
• Is the CD4 anti-TERT identifiable in hematopoietic cell donors?
• Is the CD4 anti-TERT identifiable in patients with AML in complete remission?
• Is the CD4 anti-TERT “transferable” from the donor to the recipient of hematopoietic cells at 3 months or at onset of GVHD?
• Is the CD4 anti-TERT a potential candidate biomarker of alloreactivity efficacy?

We already described 8 highly promiscuous HLA-DR and HLA-DP4 binding 15-mer peptides derived from TERT. We will assess the spontaneous anti-TERT responses by IFNγ ELISPOT after a short-term in vitro stimulation of PBMC with the mixture of the 8 selected peptides during 7 days as previously described.
As the primary objective of the study is to evaluate the landscape of telomerase-specific CD4 T-cell in the setting of alloSCT, we will require the CRYOSTEM repository as follow: pre-transplant samples with their matched sibling donors and their samples s1 or c1 if identifiable/available. Patients will be selected based on their HLA typing to ensure a correct reactivity during ELISPOT assays with our HLA classe II restricted peptides.

The report of circulating anti-telomerase T-cell in patient with AML in complete remission will be innovative and lead to consider novels targets for development of immunotherapies. Moreover, we will extend our research in patient receiving alloSCT and explore the anti-telomerase T-cell as a cellular biomarker for defining outcome after transplant. In this setting of allogeneic transplantation, our discovery might open the fields of specific immunomodulation promoting anti-telomerase response (DLI, vaccination, ex-vivo specific T-cell expansion).

Project leader
Dr Etienne Daguindau, UMR 1098 RIGHT INSERM, EFS Franche-Comté

Academic member of CRYOSTEM network

Key figures
Access to the collection : 2023
Project duration: 1 year
Number of patients involved: Selection in progress
Total number of samples: Selection in progress

Project status : samples selection in progress

Publication : NA

AstraZeneca’s goal is to analyze cancer cells from patients with T-cell acute lymphoblastic leukemia (T-cell acute lymphoblastic leukemia) in order to discover new therapies. T-ALL is a cancer of the blood and bone marrow that affects white blood cells, and for which patients can be allografted. Patient samples will be used for the detection of T-ALL related antigens. Samples will be analyzed by flow cytometry (FACS analysis) or immunohistochemistry (IHC) techniques.

Project leader
Dr Weichan Luo, Astra Zeneca

Pharmaceutical company

Country : USA

Key figures
Access to the collection : 2023
Project duration: 6 months
Number of patients involved: 10
Total number of samples: 17 (plasma)

Project status : samples selection in progress

Publication : NA