Immunomagnetic Selective Donor-derived CD4CCR7 T Cell Depletion Procedure for Peripheral Blood Stem Cells Graft

Purpose Of The Study: While acute graft-versus-host-disease (GVHD) is a T cell-mediated disease caused by alloreactive donor T cells, we and others have highlighted that patients who received higher proportion of donor CD4 naïve and central memory T cells expressing the chemokine receptor 7 (CCR7) more often developed acute GVHD than those who did not. Consequently, we then investigated in vitro the impact of selective CD4 CCR7 T cell depletion on immune reactions and showed that such a depletion reduced alloreactivity without altering acquired anti-infectious reactions. In order to translate these findings to clinic, we now developed a compliant procedure for a selective reduction of the CD4 naïve and central memory T cell subset relevant to peripheral blood stem cell (PBSC) allografts.

Patients And Methods: We performed a two-step immunomagnetic depletion of CD4 CCR7 T cells from ten G-CSF-mobilized PBSC apheresis samples.

Results: A median of 89% (82-94%) of CD4 CCR7 T cells could be depleted. This allowed a marked reduction of the alloreactive immune response against allogenic dendritic cells compared with unmanipulated cells. The preservation of CD34 cell number and the hematopoietic progenitor function were controlled. Functional tests showed that the selection procedure did not interfere with the capacity of pathogen-specific T cells to produce interferon-gamma in response to certain viral pathogens.

Conclusion: Our results pave the way to a feasible procedure that can be used in patients undergoing allo-hematopoietic cell transplantation and particularly for improving haploidentical transplant results by controlling GVHD, the main immune complication.