分析癌症患者体内疫苗诱导产生的 T 细胞。

Analysis of vaccine-induced T cells in humans with cancer.

机构信息

Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.

出版信息

Adv Exp Med Biol. 2010;684:178-88. doi: 10.1007/978-1-4419-6451-9_14.

Abstract

Over the past several years, progress in the field of tumor immunology has lead to advances in active immunotherapy and vaccination as a means ofeliciting tumor-specific immune responses to mediate tumor regression and clearance. Developing vaccines targeted against cancer became an important focus as a therapy following the success of viral vaccines in preventing infection and disease. In humans with cancer, similar to viral infections, the host immune system is capable of recognizing antigens expressed on tumor cells. This similarity allows the immunological framework of the viral vaccine to be adapted to the cancer setting in hopes of enhancing human T-cell reactivity against tumor. It is generally believed that a requirement for tumor destruction to occur is the induction of sufficient levels of immune cells with high avidity for recognition of tumor antigens. Moreover, the cells must be targeted to the tumor site and be capable of infiltrating tumor stroma.2 Several tumor-associated antigens (TAA) have been identified in the melanoma model which has allowed for immunization trials to evaluate therapeutic potential of tumor-specific T-cell induction. Some clinical trials reported limited success ofT-cell mediated tumor rejection, reportingpartial or complete regression in 10 to 30% of patients. Although tumor regression was not observed following active immunization in vivo, ex vivo assays evaluating TAA-specific T cells demonstrated tumor recognition and subsequent T-cell activation suggesting that tumor-specific T-cell induction indeed occurs but alone is not adequate to induce tumor regression. Recently, the usefulness and success of active-specific immunization (ASI) against TAAs as a means ofeliciting a tumor-specific immune response leading to tumor regression and clearance has been a topic of debate and discussion.

摘要

在过去的几年中,肿瘤免疫学领域的进展导致了主动免疫治疗和疫苗接种的进步,作为一种引发肿瘤特异性免疫反应以介导肿瘤消退和清除的方法。随着病毒疫苗在预防感染和疾病方面的成功,针对癌症的疫苗开发成为一种重要的治疗焦点。在患有癌症的人类中,类似于病毒感染,宿主免疫系统能够识别肿瘤细胞上表达的抗原。这种相似性允许将病毒疫苗的免疫学框架适应于癌症环境,以期增强人类 T 细胞对肿瘤的反应性。人们普遍认为,发生肿瘤破坏的一个要求是诱导具有高识别肿瘤抗原亲和力的足够水平的免疫细胞。此外,这些细胞必须靶向肿瘤部位并能够渗透肿瘤基质。2 在黑色素瘤模型中已经鉴定出几种肿瘤相关抗原(TAA),这使得免疫接种试验能够评估肿瘤特异性 T 细胞诱导的治疗潜力。一些临床试验报告了 T 细胞介导的肿瘤排斥的有限成功,报告了 10%至 30%的患者出现部分或完全消退。尽管在体内主动免疫接种后未观察到肿瘤消退,但评估 TAA 特异性 T 细胞的离体检测表明肿瘤识别和随后的 T 细胞激活,这表明肿瘤特异性 T 细胞诱导确实发生,但单独使用不足以诱导肿瘤消退。最近,针对 TAAs 的主动特异性免疫(ASI)作为引发导致肿瘤消退和清除的肿瘤特异性免疫反应的手段的有用性和成功已成为讨论和讨论的主题。

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