Selective T-cell depletion for haplotype-mismatched allogeneic stem cell transplantation

Abstract

Haplotype-mismatched transplantation offers a unique opportunity to treat patients without a suitable matched related or unrelated donor. Indeed, related haplo-donors are usually extremely motivated, immediately available, and can provide additional stem or immune cells when required, a most important feature in the context of high-risk malignancies. Immunomagneticallly selected CD34(+) stem cell grafts enable rapid and sustained trilineage engraftment. However, the associated delay in immune reconstitution results in significant risk for severe infectious complications and malignant relapse. The infusion of T lymphocytes selectively depleted of their anti-host reactive components represents a most interesting approach to accelerate post-transplant T-cell recovery. Such a strategy relies on ex vivo donor cell activation against host antigens and their selective elimination. Immunotoxins and magnetic beads could target antigens such as CD25 with impressive results. Photodepletion of alloreactive T cells represents an appealing alternative to both eliminate anti-host immune T cells and spare resting T cells to fight infections. Interestingly, regulatory T cells can be retained after such treatment, and have been found to transform non-regulatory into regulatory T cells, a finding that may be of utmost importance in both prevention and control of graft-versus-host disease (GVHD). Efforts to promote efficient antigen presentation and selective allodepletion promise to accelerate immune reconstitution without GVHD and to address the most crucial issues in haplo-mismatched and other types of transplants.