多发性骨髓瘤患者的CAR T细胞疗法的临床进展

Clinical Advances in CAR T Cell Therapies for the Patients with Multiple Myeloma

多发性骨髓瘤(Multiple myeloma, MM)是一种目前依然无法治愈的浆细胞恶性肿瘤。B细胞和MM细胞的小子集上表达,这使其成为用于此类疗法的合适靶抗原。在撰写本文时,来自>20项涉及抗BCMA CAR T细胞的临床试验的数据已经证明,复发性和/或难治性MM患者可以实现客观反应。这些早期研究有助于证明短期安全性和有效性;然而,大多数患者没有持续>18个月的疾病缓解。减少或延迟复发性疾病发作的尝试正在进行中,并且包括鉴定另外的CAR T细胞靶抗原和增强MM细胞上BCMA表达的方法。CAR T细胞以增强治疗的活性和安全性仍然是一种有希望的改进途径。在这篇综述中,我们总结了迄今为止进行的临床试验的数据,描述了未来可能靶向的新型抗原,并强调了未来可能提高CAR T细胞疗法疗效和/或降低其毒性的潜在创新。

Multiple myeloma (MM) is a malignancy of plasma cells that remains incurable. Expressed on a small subset of B cells and MM cells, which makes it a suitable target antigen for this type of therapy. At the time of writing, data from >20 clinical trials involving anti-BCMA CAR T cells have demon-strated that objective responses can be achieved in patients with relapsed and/or refractory MM. These early studies help demonstrate short-term safety and efficacy;However, most patients did not have remission that lasted >18 months. Attempts to reduce or delay the onset of recurrent dis-ease are ongoing and include methods to identify additional CAR T cell target antigens and enhance BCMA expression on MM cells. CAR T cells to enhance the activity and safety of treatments remains a promising avenue for improvement. In this review, we summarize data from clinical trials con-ducted to date, describe novel antigens that may be targeted in the future, and highlight potential innovations that may improve the efficacy and/or reduce the toxicity of CAR T cell therapies in the future.