Novel Immunotherapy Targets for Relapsed/Refractory B-ALL: A Literature Review.

Abstract

Objectives: B-cell acute lymphoblastic leukemia (B-ALL) is the most prevalent cancer in United States children. In recent years, immunotherapies using chimeric antigen receptors (CAR T-cells) have improved prognosis for patients with B-ALL. Previous CAR T therapies have used CD19 as a target, but loss of this protein through antigen escape may cause relapse with slim chance of remission. For patients facing relapsed/refractory B-ALL, the need for new targets is evident. In this review, we focus on the KMT2A, IKZF1-related, and DUX4r subgroups of B-ALL, highlighting proven and potential CAR T targets. With a focus on genetics, we discuss chondroitin sulfate proteoglycan 4 as a target in mixed lineage rearranged leukemia and the use of proteomic analysis to locate other B-ALL antigenic surface markers, including the targeting of CD72 within a nanobody-based framework. Additionally, we examine the thymic stromal lymphopoietin receptor as a target in B-ALL with IKAROS family zinc finger 1 deletion across various subgroups. Following this, we propose the adaptation of CD371 as a CAR T-cell target for relapsed/refractory DUX4r B-ALL in the context of promising results from studies in acute myeloid leukemia. Finally, we provide a brief overview of other relevant therapies, including tyrosine kinase inhibitors and a planned universal CAR T for off-the-shelf use, before concluding with a case study that emphasizes the necessity of novel CAR T targets.