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:Cancer Immunotherapy and Delivery System: An Update.
随着对肿瘤微环境中免疫机制的认识,免疫治疗已成为临床上治疗多种癌症的有力工具。
随着对肿瘤微环境免疫机制认识的加深,免疫治疗已成为临床上治疗多种癌症的有力工具。癌症免疫治疗主要策略包括阻断免疫检查点、过继转移工程化细胞(如T细胞、NK 细胞和巨噬细胞)、细胞因子治疗、癌症疫苗及溶瘤病毒治疗。产品价格、脱靶不良反应、免疫抑制性肿瘤微环境和癌细胞异质性等多种因素都会影响免疫治疗的疗效。此外,某些治疗(例如CAR-T 细胞治疗)治疗淋巴瘤、白血病和多发性骨髓瘤的效果优于治疗实体瘤。过去几十年来,研究人员开发了多种免疫治疗递送系统,例如纳米颗粒、水凝胶基质和可植入支架,以提高靶向免疫治疗的疗效并减少脱靶作用。本文首先总结目前常用的免疫治疗及其局限,继而概述可用于提高治疗效果、尽量降低不良反应的相关递送系统,并讨论这些系统用于癌症免疫治疗的挑战、前沿进展和应用前景。最后,本文回顾了相关方法在临床试验中的应用。
With an understanding of immunity in the tumor microenvironment, immunotherapy turns out to be a powerful tool in the clinic to treat many cancers. The strategies applied in cancer immunotherapy mainly include blockade of immune checkpoints, adoptive transfer of engineered cells, such as T cells, natural killer cells, and macrophages, cytokine therapy, cancer vaccines, and oncolytic virotherapy. Many factors, such as product price, off-target side effects, immunosuppressive tumor microenvironment, and cancer cell heterogeneity, affect the treatment efficacy of immunotherapies against cancers. In addition, some treatments, such as chimeric antigen receptor (CAR) T cell therapy, are more effective in treating patients with lymphoma, leukemia, and multiple myeloma rather than solid tumors. To improve the efficacy of targeted immunotherapy and reduce off-target effects, delivery systems for immunotherapies have been developed in past decades using tools such as nanoparticles, hydrogel matrix, and implantable scaffolds. This review first summarizes the currently common immunotherapies and their limitations. It then synopsizes the relative delivery systems that can be applied to improve treatment efficacy and minimize side effects. The challenges, frontiers, and prospects for applying these delivery systems in cancer immunotherapy are also discussed. Finally, the application of these approaches in clinical trials is reviewed.
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