Targets For CAR Therapy In Multiple Myeloma

Multiple myeloma (MM, plasma cell myeloma) is a heterogenous B-cell malignant tumor, which typically exhibits high recurrence rate, resistance to drugs and molecular diversity of tumor subclones. Given limited efficacy of standard therapy options, cellular immunotherapy featuring chimeric antigen receptor (CAR) has proven tangible potential in treatment for relapsed and refractory forms of ММ. Rational choice of a tumor target, which shows high selectivity, stable expression and biological significance, is a key to successful implementation of CAR therapy. This review has summarized and analyzed data from literature on biological properties, features of expression, and clinical development stages of CAR cell products for MM treatment, which target BCMA, GPRC5D, FcRH5, SLAMF7, CD38, CD138, TACI, APRIL, CD19, TNFR2, CD44v6, CD70, NKG2D ligands, etc. Special focus is on strategic approaches to overcoming antigenic escape, such as multi-specific CAR constructs, logical activation sequences and controlled safety systems. The analysis underscores the need for integrating molecular selection of targets with cutting-edge bioengineering solutions as a key trend for raising efficacy, stability and safety of cellular therapy in case of ММ.