Neoantigens: The Novel Precision Cancer Immunotherapy

Tiantian Zhang, Esaw Kurban, Zhe Wang
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Abstract

The past few decades have witnessed the remarkable progress of cancer immunotherapy. Neoantigens, also known as tumor-specific antigens, are novel antigens originating from tumor-specific alterations such as genomic mutations, dysregulated RNA splicing, and post-translational modifications. Neoantigens, recognized as non-self entities, trigger immune responses that evade central and peripheral tolerance mechanisms. With the notable strides in cancer genomics facilitated by next-generation sequencing technologies, neoantigens have emerged as a promising avenue for tumor-specific immunotherapy grounded in genomic profiling-based precision medicine. Furthermore, a growing number of preclinical and clinical investigations are harnessing the potential synergies between neoantigens and other immunotherapies such as adoptive cell therapy and immune checkpoint inhibitors. In this review, we will provide a comprehensive perspective encompassing the trajectory of neoantigens, neoantigen design strategies, and the diverse array of clinical applications inherent in immunotherapy strategies centered around neoantigens. Moreover, we delve into the inherent prospects and challenges that accompany the clinical adoption of neoantigen-based immunotherapies while also putting forth potential solutions to address these challenges.
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新抗原:新型精准癌症免疫疗法
在过去的几十年里,癌症免疫治疗取得了显著的进展。新抗原,也被称为肿瘤特异性抗原,是源于肿瘤特异性改变的新抗原,如基因组突变、RNA剪接失调和翻译后修饰。新抗原,被认为是非自我实体,引发免疫反应,逃避中枢和外周耐受机制。随着下一代测序技术在癌症基因组学方面的显著进步,新抗原已经成为基于基因组谱的精准医学的肿瘤特异性免疫治疗的有前途的途径。此外,越来越多的临床前和临床研究正在利用新抗原与其他免疫疗法(如过继细胞疗法和免疫检查点抑制剂)之间的潜在协同作用。在这篇综述中,我们将提供一个全面的视角,包括新抗原的发展轨迹,新抗原设计策略,以及以新抗原为中心的免疫治疗策略中固有的各种临床应用。此外,我们深入研究了伴随临床采用基于新抗原的免疫疗法的固有前景和挑战,同时也提出了解决这些挑战的潜在解决方案。
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