Allogeneic immunotherapy to optimize the graft-versus-tumor effect: concepts and controversies

Allogeneic stem cell transplantation (SCT) can be considered the most successful method of adoptive immunotherapy of cancer. It is successful in part because of the potent graft-versus-tumor (GVT) effects of the donor graft, which are independent of the conditioning regimen. This potent GVT reaction can be harnessed in some cases to treat patients who relapse after allogeneic SCT with the use of donor leukocyte infusions (DLIs). This has led to the rapid development of reduced-intensity conditioning (RIC) regimens for allogeneic SCT, an approach that relies primarily on GVT activity. However, the effects of GVT have clear disease specificity and remain associated with significant GVHD. Optimization of GVT induction will require a better understanding of the important target antigens and effector cells, as well as the development of methods that enhance GVT reactivity without excessive GVHD. The appropriate clinical setting and timing for GVT induction need to be defined more clearly, but ultimately, the immunologic control of cancer through allogeneic adoptive immunotherapy represents one of the most potent and promising therapeutic strategies for patients with hematologic malignancies.