优化移植后细胞疗法以增强血液系统恶性肿瘤中的移植物抗白血病效应

Allogeneic hematopoietic cell transplantation (HCT) can cure patients with high-risk hematologic malignancies. Donor T and natural killer (NK) cells contribute to graft-versus-leukemia (GVL) effects that provide relapse protection. Post-HCT relapses often represent inadequate GVL, but alloreactive lymphocytes that confer GVL may also cause graft-versus-host-disease (GVHD).

Here, we review recent developments to selectively augment GVL while minimizing GVHD. Insights into the unique mechanisms of post-HCT T cell dysfunction highlight interventions to enhance GVL-mediating T cells. Early clinical data suggest that adoptive transfer of engineered donor T cells, expressing either transgenic T cell receptors specific for minor histocompatibility antigens presented exclusively on recipient hematopoietic cells or chimeric antigen receptors binding surface proteins on malignant cells, can mitigate post-HCT relapse.

NK cells, key GVL mediators after haploidentical HCT, can be induced into a highly functional memory-like state and administered to HCT recipients to enhance GVL. These innovations promise much-needed improvements in post-HCT outcomes.