Guillaume Kellermann, Baharia Mograbi, Paul Hofman, Patrick Brest
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Shared epitopes create safety and efficacy concerns in several cancer vaccines.
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.
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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