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:Biological Therapies in the Treatment of Cancer-Update and New Directions.
生物疗法通过靶向癌细胞同时减少对正常组织的影响,改变了肿瘤学的面貌。
生物疗法通过靶向癌细胞并减少对正常组织的影响,改变了肿瘤学治疗格局。本文主要关注推动部分恶性肿瘤治疗进展的新型疗法。免疫疗法已反复证明其作为黑色素瘤突破性疗法的价值;采用CAR T细胞治疗B细胞急性淋巴细胞白血病(B-ALL)也对进展作出了重要贡献。目前正通过改造双特异性抗体和CAR T细胞,提高这些疗法的效率和生物利用度。溶瘤病毒疗法也在持续改进,研究者还致力于提高癌症疫苗的免疫原性和稳定性。生物疗法之间的联合,以及免疫疗法与溶瘤病毒或癌症疫苗的组合,在癌症治疗中的重要性日益增加。研究者正在积极寻找新的治疗靶点,包括免疫功能未受损的肿瘤新抗原,以及肿瘤间质细胞相关抗原。成纤维细胞活化蛋白(FAP)就是一例,其过表达见于肿瘤进展。人们也在寻找普适性治疗靶点,例如在多种癌症中都可见、作为关键遗传驱动因素的神经营养性受体酪氨酸激酶(NTRK)基因融合。本文还讨论肿瘤微环境:间质细胞可保护肿瘤细胞免受化疗影响,并促成复发和进展;同时探讨癌症干细胞治疗耐药问题及避免耐药的尝试。综述重点介绍提高生物疗法选择性的主要策略。
Biological therapies have changed the face of oncology by targeting cancerous cells while reducing the effect on normal tissue. This publication focuses mainly on new therapies that have contributed to the advances in treatment of certain malignancies. Immunotherapy, which has repeatedly proven to be a breakthrough therapy in melanoma, as well as B-ALL therapy with CAR T cells, are of great merit in this progress. These therapies are currently being developed by modifying bispecific antibodies and CAR T cells to improve their efficiency and bioavailability. Work on improving the therapy with oncolytic viruses is also progressing, and efforts are being made to improve the immunogenicity and stability of cancer vaccines. Combining various biological therapies, immunotherapy with oncolytic viruses or cancer vaccines is gaining importance in cancer therapy. New therapeutic targets are intensively sought among neoantigens, which are not immunocompromised, or antigens associated with tumor stroma cells. An example is fibroblast activation protein (FAP ), the overexpression of which is observed in the case of tumor progression. Universal therapeutic targets are also sought, such as the neurotrophic receptor tyrosine kinase (NTRK) gene fusion, a key genetic driver present in many types of cancer. This review also raises the problem of the tumor microenvironment. Stromal cells can protect tumor cells from chemotherapy and contribute to relapse and progression. This publication also addresses the problem of cancer stem cells resistance to treatment and presents attempts to avoid this phenomenon. This review focuses on the most important strategies used to improve the selectivity of biological therapies.
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