Recent Excitement in Disease Biology Seminar Series- Dr. Defu Zeng

Please join us as City of Hope Professor Dr. Defu Zeng speaks about “Prevention of graft versus host disease (GVHD) while preserving graft versus leukemia (GVL) activity”

Date: Tuesday, March 2, 2021 at 1:00pm

Location: Zoom

Abstract:

Allogeneic hematopoietic cell transplantation (Allo-HCT) is a curative therapy for hematological malignancies such as leukemia/lymphoma,  by taking advantage of alloreactive donor T cell-mediated graft versus leukemia (GVL) effect.  Unfortunately, the same alloreactive T cells also mediate a fatal side effect called graft versus host disease (GVHD). Administration of immunosuppressants can prevent GVHD but also suppress the GVL effect, leading to relapse of leukemia. Thus, prevention of GVHD while preserving GVL effect remains the  Holy Grail for allogeneic HCT. Our studies demonstrate that depletion of donor CD4+ T cells allow tissue PD-L1 interaction with PD-1 on infiltrating CD8+ T cells, resulting prevention of GVHD. Interestingly, PD-L1 interaction with CD80 in the lymphoid tissues via T-T interaction augments donor CD8+ T cell expansion and result in strong GVL effect. Furthermore, administration of tolerogenic anti-IL-2 mAb that blocks IL-2 interaction with IL-2Rb but on conventional T cells but not IL-2Ra on Treg cells augment tissue PD-L1 mediated T cell tolerance in the GVHD target tissues while preserving GVL effect in the lymphoid tissues. Therefore, administration of depleting anti-CD4 or tolerogenic anti-IL-2 mAb represent effective approaches that effectively prevent GVHD while preserving GVL effect.