Targets for CAR Therapy in Multiple Myeloma

被引:0
作者
Bezborodova, Olga A. [1 ]
Trunova, Galina V. [1 ]
Nemtsova, Elena R. [1 ]
Khokhlova, Varvara A. [1 ]
Venediktova, Julia B. [1 ]
Morozova, Natalia B. [1 ]
Vorontsova, Maria S. [1 ]
Plyutinskaya, Anna D. [1 ]
Zharova, Elena P. [1 ]
Shegai, Peter V. [1 ]
Kaprin, Andrey D. [1 ]
机构
[1] Minist Hlth Russian Federat, Moscow Hertsen Res Inst Oncol, Branch Natl Med Res Radiol Ctr, Moscow 125284, Russia
关键词
multiple myeloma; CAR-T; CAR-NK; tumor targets; immunotherapy; cellular therapy; antigen escape; multi-specific CAR; logical activation; safety of therapy; T-CELL THERAPY; TUMOR MICROENVIRONMENT; ANTI-BCMA; LEUKEMIA; DESIGN; CHALLENGES; STRATEGIES; CD56;
D O I
10.3390/ijms26136051
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Multiple myeloma (MM or plasma cell myeloma) is a heterogenous B-cell malignant tumor that typically exhibits a high recurrence rate, resistance to drugs, and molecular diversity of tumor subclones. Given the limited efficacy of standard therapy options, cellular immunotherapy featuring a chimeric antigen receptor (CAR) has proven tangible potential in treatment for relapsed and refractory forms of MM. The rational choice of a tumor target which shows high selectivity, stable expression, and biological significance is key to the successful implementation of CAR therapy. This review has summarized and analyzed data from the literature on biological properties, the features of expression, and the 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 the molecular selection of targets with cutting-edge bioengineering solutions as a key trend for raising the efficacy, stability, and safety of cellular therapy in the case of MM.
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