Neoantigen-based immunotherapies harness somatic mutations as tumor-specific targets and represent a major advance in personalized cancer treatment. Since neoantigens are presented exclusively on cancer cells, they enable highly selective T-cell recognition with minimal off-tumor toxicity. Neoantigen vaccines are rapidly emerging as a versatile class of personalized cancer immunotherapies designed to prime tumor-specific T cells by targeting somatic mutations unique to each patient’s tumor. Multiple types of neoantigen vaccines, using peptide, mRNA, and DNA, have shown feasibility, safety, and immunogenicity across diverse solid tumors. Emerging comparative data indicate that the vaccines using peptide-pulsed dendritic cells (DCs) elicit higher per-epitope CD8+T cell responses than mRNA-based vaccines, likely due to more efficient class I presentation of synthetic peptides and ex vivo-loaded DCs. In contrast, mRNAs, despite their capacity of targeting multiple neoantigen peptides simultaneously, often induce CD4+-dominant responses due to immunodominance patterns during antigen processing. Recent clinical trials in melanoma, glioblastoma, pancreatic cancer, and other types of cancer have demonstrated not only robust immune activation but also encouraging relapse-free outcomes when administered in adjuvant settings. Treatment timing strongly influenced immune responsiveness; patients with early-stage disease or those vaccinated after surgical resection generally exhibit more preserved systemic immunity and greater vaccine-induced T cell expansion compared to those with advanced disease. Future progress will rely on improved neoantigen prediction, including incorporation of post-translationally modified antigenic targets and acceleration of manufacturing pipelines to ensure timely, personalized vaccine delivery. Collectively, neoantigen vaccines offer substantial promise for integration into next-generation cancer treatment strategies.
基于新抗原的免疫疗法利用体细胞突变作为肿瘤特异性靶点,代表了个性化癌症治疗领域的重大进展。由于新抗原仅表达于癌细胞表面,能够实现高度选择性的T细胞识别,并最大程度降低对正常组织的毒性。新抗原疫苗作为一类快速发展的个性化癌症免疫疗法,通过靶向每位患者肿瘤特有的体细胞突变来激活肿瘤特异性T细胞,展现出广泛的应用前景。采用多肽、mRNA和DNA等多种形式的新抗原疫苗已在多种实体瘤中证实了其可行性、安全性和免疫原性。最新比较数据显示,采用多肽脉冲树突状细胞(DC)的疫苗比基于mRNA的疫苗能引发更强的表位特异性CD8+T细胞反应,这可能是由于合成多肽和体外负载DC能更有效地实现I类抗原呈递。相比之下,mRNA疫苗虽然能同时靶向多个新抗原表位,但在抗原加工过程中常因免疫显性模式而主要诱导CD4+T细胞反应。近期在黑色素瘤、胶质母细胞瘤、胰腺癌等癌症中的临床试验表明,在辅助治疗阶段应用新抗原疫苗不仅能引发强烈的免疫激活,还能获得令人鼓舞的无复发生存结果。治疗时机对免疫反应强度具有显著影响:与晚期患者相比,早期疾病患者或在手术切除后接种疫苗者通常表现出更完整的全身免疫状态及更强的疫苗诱导T细胞扩增。未来进展将依赖于新抗原预测技术的改进,包括整合翻译后修饰的抗原靶点,以及加速生产流程以确保及时交付个性化疫苗。总体而言,新抗原疫苗为融入下一代癌症治疗策略提供了重要前景。