肿瘤细胞治疗研究
英文原题：SOHO State-of-the-Art Updates and Next Questions | BCMA-Directed CAR T-Cells: Early Results and Future Directions.
尽管多年来不断取得的进展使多发性骨髓瘤（MM）患者的生存率得到改善，但MM在很大程度上仍无法治愈，在蛋白酶体抑制剂、免疫调节药物和抗CD38单克隆抗体治疗后进展的患者中，总生存期以月计。
尽管近年新型疗法不断涌现，多发性骨髓瘤（MM）患者生存显著改善，但MM仍基本无法治愈。蛋白酶体抑制剂、免疫调节药物和抗CD38单克隆抗体治疗后疾病进展的患者，其总生存期以月计算。对MM免疫病理学的认识加深促成了新治疗靶点的发现，如B细胞成熟抗原（BCMA）。BCMA属于肿瘤坏死因子受体超家族，表达于正常B淋巴细胞和恶性浆细胞，在正常及恶性浆细胞增殖、成熟和分化中发挥关键作用。目前，靶向BCMA抗原的抗体药物偶联物、嵌合抗原受体（CAR）T细胞和双特异性T细胞衔接器已在临床试验内外用于治疗三类药物耐药MM。本综述聚焦BCMA靶向CAR-T疗法的演变、安全性、疗效及局限性，并讨论将CAR-T细胞纳入MM治疗模式后暴露出的挑战，展望MM CAR-T疗法的未来。
Despite continued advances that have led to improved survival of patients with multiple myeloma (MM) over the years, MM remains largely incurable with overall survival in patients who have progressed after proteasome inhibitor, immunomodulatory drug, and anti-CD38 monoclonal antibody therapy measured in months. Better understanding of the immunopathology of MM has led to the discovery of newer treatment targets like B-cell maturation antigen (BCMA). BCMA is a tumor necrosis factor receptor superfamily expressed on normal B-lymphocytes and malignant plasma cells with a vital role in proliferation, maturation, and differentiation of normal and malignant plasma cells. Antibody drug conjugates, chimeric antigen receptor (CAR) T-cells and bispecific T-cell engagers targeting the BCMA antigen are now available within and outside of clinical trials for treatment of triple class refractory MM. This review article focuses on the evolution, safety, efficacy, and limitations of BCMA-directed CAR T-cell therapies. It also discusses the challenges unveiled by the incorporation of these CAR T-cells in the treatment paradigm of MM and deliberates on the future of CAR T-cell therapy within MM.
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