Ferment Benoît, Arnulf Bertrand
AP-HP, Nord/université de Paris, hôpital Saint Louis, service d'immuno-hématologie, Myosotis 4, 1, avenue Claude-Vellefaux, 75010 Paris, France.
AP-HP, Nord/université de Paris, hôpital Saint Louis, service d'immuno-hématologie, Myosotis 4, 1, avenue Claude-Vellefaux, 75010 Paris, France.
Bull Cancer. 2021 Oct;108(10S):S65-S72. doi: 10.1016/j.bulcan.2021.09.005.
Despite recent therapeutic advances, multiple myeloma remains an incurable disease and the therapeutic options currently available are insufficient in refractory patients. Chimeric antigen receptor (CAR)-expressing T cells are an innovative form of adoptive cell therapy in which T cells are reprogrammed to induce an anti-tumor response. Following the successful use of CAR-T cells in the treatment of other B-cell malignancies, CAR-T-based strategies which target the B cell maturation antigen (BCMA) on the surface of tumor plasma cell are now being used in MM patients. Idecabtagene vicleucel (ide-cel), an anti-BCMA CAR-T which has shown impressive efficacy in heavily pretreated patients, is now approved by both the FDA and EMA and is available in France through a temporary use authorization (ATU) status. However, relapses seem inevitable and strategies to delay the time to progression are being investigated. These include strategies to improve the functional persistence of CAR-T in vivo by enriching for a T memory profile and reducing their immunogenicity. In addition, since changes in BCMA expression may decrease the activity of CAR-T cells in tumor plasma cells, approaches to minimize this escape are also being studied. Finally, antigens other than BCMA on the surface of plasma cells could constitute new targets of interest for recognition by CAR-T cells. The development of CAR-T-based therapies in myeloma could lead to multiple therapeutic innovations and holds promise for eventual prolonged remissions or even cure.
尽管近期治疗取得了进展，但多发性骨髓瘤仍然是一种无法治愈的疾病，目前可用的治疗方案对难治性患者来说并不充分。嵌合抗原受体（CAR）表达的T细胞是过继性细胞治疗的一种创新形式，其中T细胞被重新编程以诱导抗肿瘤反应。在CAR-T细胞成功用于治疗其他B细胞恶性肿瘤之后，靶向肿瘤浆细胞表面B细胞成熟抗原（BCMA）的基于CAR-T的策略现在正用于多发性骨髓瘤患者。伊德凯达宾（ide-cel）是一种抗BCMA CAR-T，在经过大量预处理的患者中显示出令人印象深刻的疗效，现已获得美国食品药品监督管理局（FDA）和欧洲药品管理局（EMA）的批准，并在法国通过临时使用授权（ATU）状态上市。然而，复发似乎不可避免，目前正在研究延迟疾病进展时间的策略。这些策略包括通过富集T记忆表型和降低其免疫原性来提高CAR-T在体内的功能持久性。此外，由于BCMA表达的变化可能会降低CAR-T细胞在肿瘤浆细胞中的活性，因此也在研究尽量减少这种逃逸的方法。最后，浆细胞表面除BCMA之外的抗原可能构成CAR-T细胞识别的新的感兴趣靶点。基于CAR-T的疗法在骨髓瘤中的发展可能会带来多种治疗创新，并有望最终实现长期缓解甚至治愈。
