肿瘤新抗原特异性过继细胞免疫治疗的研究进展

Q3 Medicine
Y M Wang, B R Liu, Q Liu
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引用次数: 0

摘要

肿瘤新抗原主要是指由肿瘤突变蛋白衍生的一组特定的肿瘤抗原,但也包括整合到基因组中的致瘤病毒产生的抗原,这些抗原在人体正常细胞中不表达,但在肿瘤细胞中特异性表达,能够触发宿主的肿瘤特异性细胞免疫和体液免疫。近年来,肿瘤免疫治疗取得了重大进展,如治疗性肿瘤疫苗和过继细胞治疗(ACT)。然而,独立的肿瘤治疗疫苗有几个缺点。它们具有低免疫原性,面临巨大的肿瘤负担,并且对免疫抑制微环境高度敏感。因此,在临床实践中孤立应用时,其治疗效果仍然有限。与免疫检查点抑制剂和肿瘤疫苗等免疫疗法相比,ACT受体内免疫抑制微环境的影响较小,可以产生足够数量的杀伤细胞。ACT的关键在于产生免疫原性肿瘤特异性杀伤细胞。新抗原增强ACT的免疫原性和抗肿瘤特异性。其中,主要总结了针对ERBB2IP、KRAS、TP53等突变基因突变的ACT,以及来源于eb病毒、人乳头瘤病毒等病毒的ACT。并对新抗原特异性ACT存在的问题及相应对策进行了总结和探讨。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
[Research progress of tumor neoantigen-specific adoptive cellular immunotherapy].

Tumour neoantigen sprimarily refer to a specific group of tumour antigens derived from tumour mutant proteins, but also including antigens generated by the oncogenic viruses integrated into the genome, which are not expressed by normal cells in the human body but are specifically expressed in tumor cells, and are capable of triggering the tumour-specific cellular and humoral immunity in the host. In recent years, significant advances in tumor immunotherapy such as therapeutic oncology vaccines, and adoptive cell therapy (ACT) have been acquired. However, standalone tumor therapeutic vaccines exhibit several drawbacks. They possess low immunogenicity, face a substantial tumor burden, and are highly susceptible to the immunosuppressive microenvironment. Consequently, when applied in isolation during clinical practice, their therapeutic efficacy remains limited. Compared with immunotherapies such as immune checkpoint inhibitors and tumor vaccines, ACT is less affected by the immunosuppressive microenvironment in the body and can generate a sufficient number of killer cells. The crux of ACT lies in the generation of immunogenic tumor-specific killer cells. Neoantigens enhance the immunogenicity and anti-tumor specificity of ACT. Among them, the ACT targeting mutant gene mutations, including ERBB2IP, KRAS and TP53, as well as those derived from viruses such as Epstein-Barr virus (EBV) and human papillomavirus (HPV), is primarily summarized. Moreover, the existing issues of neoantigen-specific ACT and corresponding countermeasures are summarized and discussed.

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来源期刊
中华肿瘤杂志
中华肿瘤杂志 Medicine-Medicine (all)
CiteScore
1.40
自引率
0.00%
发文量
10433
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