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Targets for CAR Therapy in Multiple Myeloma
Olga A Bezborodova1, Galina V Trunova1, Elena R Nemtsova1
1Moscow Hertsen Research Institute of Oncology-Branch of the National Medical Radiology Research Center, Ministry of Health of the Russian Federation, Moscow 125284, Russia.
Abstract:
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.
Insights
Chimeric antigen receptor (CAR) T-cell therapy shows promise for multiple myeloma (MM). Optimizing target selection and employing advanced bioengineering strategies are crucial for enhancing CAR T-cell therapy
Area of Science:
- Oncology
- Immunology
- Biotechnology
Background:
- Multiple myeloma (MM) is a complex B-cell malignancy characterized by high recurrence and drug resistance.
- Current standard therapies have limited efficacy, driving the need for novel treatment approaches.
- Chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising strategy for relapsed and refractory MM.
Purpose of the Study:
- To review and analyze CAR T-cell therapy targets for multiple myeloma.
- To evaluate the biological properties, expression patterns, and clinical development of CAR cell products.
- To explore strategies for overcoming challenges such as antigenic escape in CAR T-cell therapy for MM.
Main Methods:
- Comprehensive literature review of CAR T-cell therapy targets in MM.
- Analysis of biological characteristics and clinical data for various CAR constructs.
- Evaluation of advanced approaches like multi-specific CARs and safety systems.
Main Results:
- Identified and analyzed numerous CAR T-cell targets for MM, including BCMA, GPRC5D, FcRH5, SLAMF7, CD38, and others.
- Highlighted the importance of target selectivity, stable expression, and biological relevance.
- Discussed strategies to mitigate antigenic escape, such as multi-specific CARs and controlled activation.
Conclusions:
- The rational selection of targets and innovative bioengineering are critical for effective CAR T-cell therapy in MM.
- Integrating molecular target insights with advanced engineering solutions will improve efficacy, durability, and safety.
- CAR T-cell therapy holds significant potential for improving outcomes in relapsed and refractory multiple myeloma.
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