Multiple myeloma (MM) is a nearly always incurable malignancy of plasma cells, so new approaches to treatment are needed. T-cell therapies are a promising approach for treating MM, with a mechanism of action different than those of standard MM treatments. Chimeric antigen receptors (CARs) are fusion proteins incorporating antigen-recognition domains and T-cell signaling domains. T cells genetically engineered to express CARs can specifically recognize antigens. Success of CAR-T cells (CAR-Ts) against leukemia and lymphoma has encouraged development of CAR-T therapies for MM. Target antigens for CARs must be expressed on malignant cells, but expression on normal cells must be absent or limited. B-cell maturation antigen is expressed by normal and malignant plasma cells. CAR-Ts targeting B-cell maturation antigen have demonstrated significant antimyeloma activity in early clinical trials. Toxicities in these trials, including cytokine release syndrome, have been similar to toxicities observed in CAR-T trials for leukemia. Targeting postulated CD19+ myeloma stem cells with anti-CD19 CAR-Ts is a novel approach to MM therapy. MM antigens including CD138, CD38, signaling lymphocyte-activating molecule 7, and κ light chain are under investigation as CAR targets. MM is genetically and phenotypically heterogeneous, so targeting of >1 antigen might often be required for effective treatment of MM with CAR-Ts. Integration of CAR-Ts with other myeloma therapies is an important area of future research. CAR-T therapies for MM are at an early stage of development but have great promise to improve MM treatment.

中文翻译：

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多发性骨髓瘤的嵌合抗原受体 T 细胞疗法


多发性骨髓瘤 (MM) 是一种几乎无法治愈的浆细胞恶性肿瘤，因此需要新的治疗方法。 T 细胞疗法是治疗 MM 的一种有前景的方法，其作用机制与标准 MM 治疗不同。嵌合抗原受体 (CAR) 是包含抗原识别结构域和 T 细胞信号传导结构域的融合蛋白。经过基因工程改造后表达 CAR 的 T 细胞可以特异性识别抗原。 CAR-T 细胞 (CAR-T) 对抗白血病和淋巴瘤的成功鼓励了 MM CAR-T 疗法的开发。 CAR 的靶抗原必须在恶性细胞上表达，但在正常细胞上必须不表达或表达有限。 B 细胞成熟抗原由正常和恶性浆细胞表达。靶向 B 细胞成熟抗原的 CAR-T 在早期临床试验中已表现出显着的抗骨髓瘤活性。这些试验中的毒性（包括细胞因子释放综合征）与白血病 CAR-T 试验中观察到的毒性相似。使用抗 CD19 CAR-T 靶向假定的 CD19+ 骨髓瘤干细胞是一种新的 MM 治疗方法。包括 CD138、CD38、信号淋巴细胞激活分子 7 和 κ 轻链在内的 MM 抗原正在作为 CAR 靶标进行研究。 MM 在遗传和表型上具有异质性，因此，为了使用 CAR-T 有效治疗 MM，通常可能需要靶向 >1 种抗原。 CAR-T 与其他骨髓瘤疗法的整合是未来研究的一个重要领域。 MM 的 CAR-T 疗法尚处于开发的早期阶段，但在改善 MM 治疗方面具有巨大的前景。