Adoptive T-cell therapy for Leukemia

Abstract

Allogeneic stem cell transplantation (alloSCT) is the most robust form of adoptive cellular therapy (ACT) and has
been tremendously effective in the treatment of leukemia. It is one of the original forms of cancer immunotherapy
and illustrates that lymphocytes can specifically recognize and eliminate aberrant, malignant cells. However, because of
the high morbidity and mortality that is associated with alloSCT including graft-versus-host disease (GvHD), refining the
anti-leukemia immunity of alloSCT to target distinct antigens that mediate the graft-versus-leukemia (GvL) effect could
transform our approach to treating leukemia, and possibly other hematologic malignancies. Over the past few decades,
many leukemia antigens have been discovered that can separate malignant cells from normal host cells and render
them vulnerable targets. In concert, the field of T-cell engineering has matured to enable transfer of ectopic high-affinity
antigen receptors into host or donor cells with greater efficiency and potency. Many preclinical studies have
demonstrated that engineered and conventional T-cells can mediate lysis and eradication of leukemia via one or
more leukemia antigen targets. This evidence now serves as a foundation for clinical trials that aim to cure leukemia
using T-cells. The recent clinical success of anti-CD19 chimeric antigen receptor (CAR) cells for treating patients with
acute lymphoblastic leukemia and chronic lymphocytic leukemia displays the potential of this new therapeutic
modality. In this review, we discuss some of the most promising leukemia antigens and the novel strategies
that have been implemented for adoptive cellular immunotherapy of lymphoid and myeloid leukemias. It is
important to summarize the data for ACT of leukemia for physicians in-training and in practice and for investigators
who work in this and related fields as there are recent discoveries already being translated to the patient setting and
numerous accruing clinical trials. We primarily focus on ACT that has been used in the clinical setting or that is currently
undergoing preclinical testing with a foreseeable clinical endpoint.