决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Overcoming the challenges encountered in CAR-T therapy: latest updates from the 2023 ASH annual conference.
嵌合抗原受体(CAR)-T 细胞疗法已进入突破时代,其特征是治疗机遇与挑战并存。
嵌合抗原受体(CAR)T 细胞疗法已进入突破性发展阶段,同时伴随着治疗机遇和挑战。随着基因编辑技术的结合,CAR-T 细胞有望成为清除肿瘤细胞的强效“战士”,并攻击多种肿瘤,包括 T 细胞恶性肿瘤和急性髓系白血病。优化 CAR-T 的疗效、安全性和生产速度,并结合放疗、造血干细胞移植、小分子抑制剂和双特异性抗体等治疗策略,可能彻底改变肿瘤治疗格局。因此,下一代细胞免疫疗法,包括通用 CAR-NK 细胞和协同联合方案,预计将在未来十年显著影响癌症治疗。不过,CAR-T 治疗失败率仍然较高。挑战在于确定最佳联合策略,并找到可靠、稳健的生物标志物,以有效识别最有可能从 CAR-T 中获益的患者。本文重点介绍 2023 年美国血液学会年会上报告的 CAR-T 产品、联合治疗策略和应答预测生物标志物的最新创新。
Chimeric antigen receptor (CAR) -T cell therapy has entered the breakthrough era, characterized by a blend of therapeutic opportunities and challenges. With the integration of genome-editing technology, CAR-T cells will be empowered to become super warriors in eradicating tumor cells and attacking various tumors, including T-cell malignancies and acute myeloid leukemia. Notably, the optimization of CAR-T cells, including efficacy, safety, and manufacturing speed, coupled with other therapeutic strategies such as radiotherapy, hematopoietic stem cell transplantation, small-molecule inhibitors, and bispecific antibodies, could revolutionize the therapeutic landscape of tumors. Consequently, next-generation cellular immunotherapy, including universal CAR-NK cells and synergistic combination approaches, are anticipated to significantly impact cancer treatment in the coming decade. Nevertheless, the failure rates of CAR-T therapy continue to be significant. The challenge lies in determining the optimal combination strategy and identifying reliable and robust biomarkers to effectively select the patients who will derive the greatest benefit from CAR-T therapy. Herein, we highlight recent innovations in CAR-T products, combination strategies and predictive biomarkers of response presented at the 2023 ASH Annual Meeting.
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