T cell optimization for graft-versus-leukemia responses
Melinda A. Biernacki, Vipul S. Sheth, Marie Bleakley
Melinda A. Biernacki, Vipul S. Sheth, Marie Bleakley
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T cell optimization for graft-versus-leukemia responses

Abstract

Protection from relapse after allogeneic hematopoietic cell transplantation (HCT) is partly due to donor T cell–mediated graft-versus-leukemia (GVL) immune responses. Relapse remains common in HCT recipients, but strategies to augment GVL could significantly improve outcomes after HCT. Donor T cells with αβ T cell receptors (TCRs) mediate GVL through recognition of minor histocompatibility antigens and alloantigens in HLA-matched and -mismatched HCT, respectively. αβ T cells specific for other leukemia-associated antigens, including nonpolymorphic antigens and neoantigens, may also deliver an antileukemic effect. γδ T cells may contribute to GVL, although their biology and specificity are less well understood. Vaccination or adoptive transfer of donor-derived T cells with natural or transgenic receptors are strategies with potential to selectively enhance αβ and γδ T cell GVL effects.

Authors

Melinda A. Biernacki, Vipul S. Sheth, Marie Bleakley

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Figure 2

Illustration of 3 PBSC graft engineering strategies to reduce GVHD.

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Illustration of 3 PBSC graft engineering strategies to reduce GVHD. (A) ...
(A) In pan-T cell–depleted (pan-TCD) grafts, only CD34+ HSCs (purple) that have been positively selected from donor PBSCs are infused into the recipient. (B) In naive T cell–depleted grafts, CD34+ HSCs are first isolated from PBSCs by positive selection as in A. The CD34– fraction is then depleted of CD45RA+ cells, which removes CD45RA+ naive T cells. The CD34+ HSC and CD45RA– fractions (CD4+CD3+ Tm, dark green; CD8+CD3+ Tm, dark blue; iNKT, yellow) are then infused into the recipient. (C) In αβ T cell–depleted (αβ-TCD) grafts, donor PBSCs are depleted of αβ TCR+ cells and often CD19+ cells, which removes αβ T cells and iNKT cells, and B cells, respectively. The αβ TCR–CD19– fraction, including NK (red with granules) and γδ (orange with TCR) T cells, is infused into the recipient. Illustrated by Rachel Davidowitz.