A program of international researchConquering the 3 families of complications
Calls for projects
Since the lifting of its embargo in April 2015, CRYOSTEM has regularly launched calls for projects within the international scientific community with one objective: to better understand the biology of the complications of HSCT (which also constitutes an excellent opportunity to explore, as true to life as possible, many challenges in contemporary immunology and cancer) and in turn to better prevent, diagnose and treat these complications.
Today, to accelerate these discoveries, CRYOSTEM is giving access to 148,000 biological samples of transplant donor-recipient pair in its collection to academic and industrial laboratories from around the world. Initially focused on the single disease of graft-versus-host (Graft versus Host Disease or GvHD), the scope was further extended in November 2016 to all the complications of HSCT (with the authorization of the Committee of the Protection of Persons – CPP – South Mediterranean I).
The first research projects retained by cryostem and having access to the collection:
Identifying at-risk patients
A new class of immune cells to predict GvHD?
Graft-versus-host disease (GvHD) remains the main cause of death after a hematopoietic stem cell transplant and to date, clinicians have no means of predicting this complication.
The teams of Professor Eric VIVIER¹,² and Dr Frédéric VELY¹,²,³ are currently working on a new category of immune cells that could suggest a way forward: Innate Lymphoid Cells (ILCs). Located in preference in the mucous membranes (intestine, lung, skin…), they are on the front line to respond rapidly to any perturbation in the environment. Preliminary results on some samples from patients suggest that after the transplant the appearance of certain subpopulations of ILCs may be associated with a lower risk of GvHD. Today, through two studies, researchers and clinicians are trying to validate this hypothesis.
“Natural Killer Cells and Innate Immunity” Laboratory, Marseille-Luminy Center for Immunology (Inserm, CNRS, AMU)¹
Immunology Laboratory, Conception Hospital (AP-HM)² Immuno-profiling platform, Marseille Immunopole³
Project duration: 1 year
Number of patients involved: 124
Total number of samples: 1 056
Project amount: € 33,556
Reducing the risk
Are other atypical white blood cells an asset to address complications?
MAIT cells (Mucosal-Associated Invariant T cells) are another atypical subpopulation of white blood cells. Morphologically, they resemble T lymphocytes of the immunity memory and, similarly, they possess surface radars that allow them to recognize specifically the pathogens to eliminate. However the similarity ends there. Whereas the first only activate and multiply after having found the pathogen in specialized places, the MAIT cells are immediately in “attack” mode, on the lookout for the places where the pathogens circulate: blood, intestinal mucosa, liver and lungs. There, they kill all bacteria and infected cells and release chemical molecules that will mobilize other partners of the immune response.
The teams of Professors Jean-Hugues DALLE¹ and Sophie CAILLAT-ZUCMAN² are today attempting to answer two questions: depending on the packaging they have received, do all patients have the same capacity to reconstitute their stock of MAIT cells? Are those that rapidly cover MAIT cells better equipped to fight GvHD and infections?
Pediatric Hematology-Oncology Unit, Robert Debré Hospital (AP-HP)¹ “Innate Immunity in Children” Laboratory, Center of Research on Inflammation (Inserm, CNRS, Paris Diderot University)²
Project duration: 1 year
Number of patients involved: 55
Total number of samples: 468
Project amount: € 19,521
Better diagnosing and monitoring GvHD
What biomarkers for diagnosis and monitoring of treatment of GvHD?
The transplant provides the patient not only with blood stem cells but also inevitably with more mature immune cells, susceptible to attack the body’s own tissue. To prevent this reaction, doctors maximize the compatibility between the donor and the recipient and stop, for a time, the patient’s immune system by means of an immunosuppressive therapy. GvHD remains nonetheless the main complication of the transplant. Less frequent, the acute form appears just after the transplant, the chronic form occurring some months later (preceded or not by an acute form of GvHD). In both cases, the graft lymphocytes attack the patient’s organs: mucosa, skin, liver and lungs. An “autoimmune disease” that immunosuppressants often manage to control at the expense of an increased susceptibility to infections.
Today, the doctor confirms his diagnosis by analyzing the biopsy of the diseased organ. The team of Professor Pierre-Simon ROHRLICH¹,² and Dr Etienne DAGUINDAU¹,² are attempting to validate the first blood markers that could rationalize the diagnosis and treatment follow-up of GvHD.
Pediatric Hematology-Oncology Unit, Archet Hospital, Univeristy Hospital of Nice¹
Department of Pediatrics, Blood Marrow and Stem Cell Transplant, Indiana University Melvin and Bren Simon Cancer Center, Indianapolis², USA
Project duration: 2 years
Number of patients involved: 227
Total number of samples: 500
Project amount: € 25,608