CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:The preclinical discovery and clinical development of ciltacabtagene autoleucel (Cilta-cel) for the treatment of multiple myeloma.
The preclinical discovery and clinical development of ciltacabtagene autoleucel (Cilta-cel) for the treatment of multiple myeloma.
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现代新一代免疫治疗正在持续改变 MM 的治疗格局。尽管 CAR-T 细胞疗法存在若干局限性,包括毒性、成本和可及性有限,但 MM 的长期无病生存期乃至潜在治愈终于触手可及。
尽管过去二十年取得了显著的治疗进展,使患者生存率得到极大改善,但多发性骨髓瘤(MM)仍被认为是一种不可治愈的疾病。因此,亟需新的治疗策略。基因工程/重定向嵌合抗原受体(CAR)T细胞可能代表癌症免疫治疗中最引人注目的方式,对MM尤其如此。事实上,前所未有的缓解率促成了首批两种BCMA靶向CAR-T 细胞产品idecabtagene-vicleucel(“Ide-cel”)和ciltacabtagene-autoleucel(“Cilta-Cel”)近期获批,用于治疗经过大量预处理的MM患者。此外,两者也正在成为更早期治疗线中的新标准治疗。涵盖领域:本文简要回顾了CAR-T 细胞临床前开发的历史,特别关注Cilta-cel。此外,本文总结了关于Cilta-cel的最新临床数据,并讨论了进一步提高其活性和降低其毒性的策略。
INTRODUCTION: Despite remarkable therapeutic advances over the last two decades, which have resulted in dramatic improvements in patient survival, multiple myeloma (MM) is still considered an incurable disease.
Therefore, there is a high need for new treatment strategies. Genetically engineered/redirected chimeric antigen receptor (CAR) T cells may represent the most compelling modality of immunotherapy for cancer treatment in general, and MM in particular. Indeed, unprecedented response rates have led to the recent approvals of the first two BCMA-targeted CAR T cell products idecabtagene-vicleucel ('Ide-cel') and ciltacabtagene-autoleucel ('Cilta-Cel') for the treatment of heavily pretreated MM patients.
In addition, both are emerging as a new standard-of-care also in earlier lines of therapy. AREAS COVERED: This article briefly reviews the history of the preclinical development of CAR T cells, with a particular focus on Cilta-cel.
Moreover, it summarizes the newest clinical data on Cilta-cel and discusses strategies to further improve its activity and reduce its toxicity. EXPERT OPINION: Modern next-generation immunotherapy is continuously transforming the MM treatment landscape. Despite several caveats of CAR T cell therapy, including its toxicity, costs, and limited access, prolonged disease-free survival and potential cure of MM are finally within reach.
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