Immunomagnetic selective donor-derived CD4+CCR7+ T cell depletion procedure for peripheral blood stem cells graft

Abstract

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.

Keywords: Graft engineering; Graft-versus-host disease; Naïve T cells; Selective T cell depletion; T-Lymphocyte Subsets.