Allogeneic Hematopoietic Stem Cell (HSC) Transplantation Clinical Trial
Official title:
Expansion of Invariant NKT Cells for a Cell Immunotherapeutic Approach Allowing the Control of Graft Versus Host-disease and Preserving the Graft Versus Leukemia Effect After Allogeneic Hematopoietic Stem Cell Transplantation
Allogeneic hematopoietic stem cell (HSC) transplantation remains the most efficient cellular
immunotherapeutic approach for the treatment of myeloid hematological malignancies. However,
its use is hampered by the risk of developing acute graft-versus-host disease (aGVHD).
Invariant NKT cells (iNKT) represent a good candidate of immuno-regulatory cells that could
control GVHD while preserving the anti-leukemic effect (GVL) of HSCT. Our team have shown
that higher numbers and expansion capacity of CD4- iNKT cells contained in the HSC graft were
associated with reduced risk of aGVHD but preserved GVL effect and that some healthy donors
have low numbers and expansion capacity CD4- iNKT cells 1.
The objective of this project is to develop a strategy allowing to expand human CD4- iNKT
cells from healthy donors of HSC grafts that would be transposable to GMP-validated cell
production. Our team proposes to first determine the best strategy to expand the CD4- iNKT
cell subset from G-SCF mobilized peripheral blood stem cells (PBSC) obtained from healthy
donors, at little scale using cultures GMP validated conditions, by comparing the convention
expansion protocol using IL-2 alone to IL-7, IL-15, IL-4 or combination of those cytokines
involved in the expansion of T cells and by culturing the cells in a bioreactor. Our team
will then explore the characteristics of cells after expansion in terms of phenotype,
transcription signature and functions in vitro (in mixed lymphocyte reaction) and in vivo in
a well-established xenogeneic model of GVHD.
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