Shared epitopes create safety and efficacy concerns in several cancer vaccines.

IF 10.3 1区 医学 Q1 IMMUNOLOGY
Guillaume Kellermann, Baharia Mograbi, Paul Hofman, Patrick Brest
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引用次数: 0

Abstract

Tumor-associated antigens (TAAs) are the targets of several therapeutic cancer vaccines. However, many TAAs contain epitopes identical to unintended targets, creating shared epitopes with other human proteins in normal tissues. Moreover, for some TAAs like ASCL2, KLK2, TPTE, CLDN6, and PSMA, the off-targeted proteins are often expressed at a higher level in healthy tissues than the target in cancer, potentially impacting both the safety and the efficacy of T cell immunity. Altogether, our analysis indicates a suboptimal design of several cancer vaccines currently in clinical development: ATP128, BNT111, BNT112, BNT116, INO-5401. We recommend that next-generation cancer vaccines should integrate rigorous epitope filtering strategies to eliminate shared sequences in TAAs.

共享表位在几种癌症疫苗中引起安全性和有效性问题。
肿瘤相关抗原(TAAs)是几种治疗性癌症疫苗的靶点。然而,许多taa含有与意外目标相同的表位,与正常组织中的其他人类蛋白质形成共享的表位。此外,对于一些TAAs,如ASCL2、KLK2、TPTE、CLDN6和PSMA,脱靶蛋白在健康组织中的表达水平往往高于肿瘤中的靶蛋白,这可能会影响T细胞免疫的安全性和有效性。总之,我们的分析表明,目前正在临床开发的几种癌症疫苗(ATP128、BNT111、BNT112、BNT116、INO-5401)的设计不理想。我们建议下一代癌症疫苗应整合严格的表位过滤策略,以消除taa中的共享序列。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal for Immunotherapy of Cancer
Journal for Immunotherapy of Cancer Biochemistry, Genetics and Molecular Biology-Molecular Medicine
CiteScore
17.70
自引率
4.60%
发文量
522
审稿时长
18 weeks
期刊介绍: The Journal for ImmunoTherapy of Cancer (JITC) is a peer-reviewed publication that promotes scientific exchange and deepens knowledge in the constantly evolving fields of tumor immunology and cancer immunotherapy. With an open access format, JITC encourages widespread access to its findings. The journal covers a wide range of topics, spanning from basic science to translational and clinical research. Key areas of interest include tumor-host interactions, the intricate tumor microenvironment, animal models, the identification of predictive and prognostic immune biomarkers, groundbreaking pharmaceutical and cellular therapies, innovative vaccines, combination immune-based treatments, and the study of immune-related toxicity.
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