The Problem of Molecular Target Choice for CAR-T Cells in Acute Myeloid Leukemia Therapy

Abstract

Recently, the chimeric antigen receptor (CAR)-T approach represented a breakthrough in the treatment of B-cell malignancies, encouraging the application of the approach for other hematological diseases, such as acute myeloid leukemia (AML). Heterogeneity and antigen variation in the pathological cell population hinder the choice of molecular targets in the case of AML. In this review, the critical aspects were described that are usually considered when selecting molecular targets for the new CAR genetic constructs. The role of AML-associated antigens in AML progression was covered. In conclusion, we proposed an approach that may allow the elimination of pathological cells in AML more effectively.

Keywords: CAR T; acute myeloid leukemia; target choice.

Figure 1

Challenges of molecular target choice for CAR-T cells in AML. (A) Heterogeneity of blast cells limits the effectiveness of CAR-T cell therapy of AML. (B) The AML-associated antigens are often expressed by the healthy cells, leading to CAR-T-mediated on-target off-tumor toxicity. CAR; chimeric antigen receptor. AML; acute myeloid leukemia.

Figure 2

Heterogenic blast population in AML may be targeted with a cocktail of CAR-Ts, each specific to an AML-associated antigen expressed by a pathological subpopulation.