Division of Hematologic Malignancies and Cellular Therapy, Duke University Medical Center, Durham, NC, USA.
Division of Hematologic Malignancies and Cellular Therapy, Duke University Medical Center, Durham, NC, USA.
Pharmacol Ther. 2022 Apr;232:108007. doi: 10.1016/j.pharmthera.2021.108007. Epub 2021 Sep 25.
Although treatment outcomes of multiple myeloma patients have improved significantly during the last two decades, myeloma is still an incurable disease. There are newly emerging immunotherapies to treat multiple myeloma including monoclonal antibodies, antibody-drug conjugate, bispecific antibodies, and chimeric antigen receptor (CAR) T cell therapy. Impressive response rate and clinical efficacy in heavily pretreated myeloma patients led to the FDA approval of the first myeloma CAR-T therapy in March 2021. Among many different targets for myeloma CAR-T therapies, B Cell Maturation Antigen (BCMA) has been the most successful target so far, but other targets which can be used either for single-target or dual-target CAR-T's are actively being explored. Clinical efficacy and safety of current myeloma CAR-T therapies will be presented here. Potential mechanisms leading to resistance include clearance of CAR-T cells, antigenic escape, and immunosuppressive tumor microenvironment. Novel strategies to enhance myeloma CAR-T will also be described. In this article, we provide a comprehensive review of the current data and the future directions of myeloma CAR-T therapies.
虽然多发性骨髓瘤患者的治疗结果在过去二十年中显著改善,但骨髓瘤仍然是一种不可治愈的疾病。目前有新出现的免疫疗法来治疗多发性骨髓瘤,包括单克隆抗体、抗体药物偶联物、双特异性抗体和嵌合抗原受体 (CAR) T 细胞疗法。在经过大量预处理的骨髓瘤患者中,令人印象深刻的缓解率和临床疗效导致 FDA 在 2021 年 3 月批准了首个骨髓瘤 CAR-T 疗法。在骨髓瘤 CAR-T 疗法的众多不同靶点中,B 细胞成熟抗原 (BCMA) 是迄今为止最成功的靶点,但其他可用于单靶点或双靶点 CAR-T 的靶点也在积极探索中。本文将介绍目前骨髓瘤 CAR-T 疗法的临床疗效和安全性。导致耐药的潜在机制包括 CAR-T 细胞清除、抗原逃逸和免疫抑制肿瘤微环境。还将描述增强骨髓瘤 CAR-T 的新策略。本文全面综述了骨髓瘤 CAR-T 疗法的现有数据和未来方向。
Pharmacol Ther. 2022-4
Front Immunol. 2022
Bull Cancer. 2021-10
Leuk Lymphoma. 2024-2
Expert Opin Biol Ther. 2019-7-11
Cancer Lett. 2023-1-28
Best Pract Res Clin Haematol. 2021-9
J Oncol Pharm Pract. 2022-6
Life (Basel). 2024-4-1
Ther Adv Hematol. 2024-3-13
Front Immunol. 2023
Recent Pat Anticancer Drug Discov. 2024
N Engl J Med. 2021-2-25
J Hematol Oncol. 2020-12-3
Cancer Immunol Res. 2020-12