Hepatocellular carcinoma (HCC), the most prevalent form of primary liver cancer, presents significant therapeutic challenges due to its molecular complexity, late-stage diagnosis, and inherent resistance to conventional treatments. The intermediate to low mutational burden in HCC and its ability to evade the immune system through multiple mechanisms complicate the development of effective therapies. Recent advancements in immunotherapy, particularly neoantigen-based vaccines, offer a promising, personalized approach to HCC treatment. Neoantigens are tumor-specific peptides derived from somatic mutations in tumor cells. Unlike normal cellular antigens, neoantigens are foreign to the immune system, making them highly specific targets for immunotherapy. Neoantigens arise from genetic alterations such as point mutations, insertions, deletions, and gene fusions, which are expressed as neoepitopes that are not present in healthy tissues, thus evading the immune tolerance mechanisms that typically protect normal cells. Preclinical and early-phase clinical studies of neoantigen-based vaccines have shown promising results, demonstrating the ability of these vaccines to elicit robust T cell responses against HCC. The aim of the current review is to provide an in-depth exploration of the therapeutic potential of neoantigen-based vaccines in HCC, focusing on neoantigen identification, vaccine platforms, and their integration with immune checkpoint inhibitors to enhance immunogenicity. It also evaluates preclinical and clinical data on efficacy and safety while addressing challenges in clinical translation. By taking advantage of the unique antigenic profile of each patient’s tumor, neoantigen-based vaccines represent a promising approach in the treatment of HCC, offering the potential for improved patient outcomes, long-term remission, and a shift towards personalized, precision medicine in liver cancer therapy.
肝细胞癌（HCC）作为原发性肝癌中最常见的类型，因其分子复杂性、诊断时多已进展至晚期以及对传统治疗存在固有耐药性，构成了显著的治疗挑战。HCC的中低突变负荷及其通过多种机制逃避免疫系统的能力，使得有效疗法的开发变得尤为复杂。近年来免疫治疗领域的进展，尤其是基于新抗原的疫苗，为HCC治疗提供了一种前景广阔的个体化策略。新抗原是源自肿瘤细胞体细胞突变的肿瘤特异性肽段。与正常细胞抗原不同，新抗原对免疫系统而言是“外来物”，这使其成为免疫治疗的高度特异性靶点。新抗原产生于点突变、插入、缺失和基因融合等遗传改变，这些改变表达为健康组织中不存在的“新表位”，从而绕过了通常保护正常细胞的免疫耐受机制。基于新抗原的疫苗在临床前及早期临床研究中已显示出鼓舞人心的结果，证明了这些疫苗能够引发针对HCC的强效T细胞反应。本综述旨在深入探讨基于新抗原的疫苗在HCC中的治疗潜力，重点关注新抗原的鉴定、疫苗平台技术及其与免疫检查点抑制剂的联合应用以增强免疫原性。同时，文章评估了相关疗效和安全性的临床前及临床数据，并探讨了临床转化面临的挑战。通过利用每位患者肿瘤独特的抗原谱，基于新抗原的疫苗代表了一种极具前景的HCC治疗方法，有望改善患者预后、实现长期缓解，并推动肝癌治疗向个体化、精准医疗的方向转变。
Personalized Immunity: Neoantigen-Based Vaccines Revolutionizing Hepatocellular Carcinoma Treatment
肿瘤(癌症)患者之家