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mRNA疫苗在癌症免疫治疗中的应用

Application of mRNA vaccines in cancer immunotherapy

  • 摘要: 癌症发病率与死亡率攀升,传统疗法局限性凸显,亟需更精准的免疫治疗方法。mRNA疫苗因其在抗原设计、生产和安全性上的优势,成为癌症免疫治疗领域的研究热点。本文综述了mRNA癌症疫苗的分子设计优化(如核苷修饰、UTR和ORF优化以增效和稳定)、关键抗原类型(包括病毒抗原、肿瘤相关抗原TAA、肿瘤特异性抗原TSA/新抗原及免疫调节因子)、递送系统以及临床研究进展。该类疫苗通过在体内表达特定抗原,激活免疫系统以识别和清除癌细胞。目前已有多种mRNA疫苗进入临床试验,常联用免疫检查点抑制剂等。尽管其有很好的应用前景,但仍面临mRNA不稳定性、靶向递送困难、免疫耐受和肿瘤逃逸等挑战,未来需在抗原预测、靶向递送载体及联合用药上持续突破。

     

    Abstract: With the increasing incidence and mortality of cancer, the limitations of conventional therapies have become increasingly apparent, necessitating the development of more precise immunotherapeutic approaches. mRNA vaccines have emerged as a prominent research focus in cancer immunotherapy due to their advantages in antigen design, rapid production, and enhanced safety profiles. This article reviews the advances in molecular design optimization of mRNA cancer vaccines such nucleoside modification, 5’-/3’-untranslated region (UTR) optimization and open reading frame (ORF) engineering to enhance efficacy and stability), key antigen types (viral antigens, tumor-associated antigens, tumor-specific antigens, and immunomodulators), delivery systems, and clinical research. By expressing specific antigens in vivo, these vaccines activate immune recognition and elimination of cancer cells. Currently, multiple mRNA vaccines have entered clinical trials, often in combination with immune checkpoint inhibitors or other immunotherapies. Despite their promising potential, challenges such as mRNA instability, difficulty in targeted delivery, immune tolerance, and tumor immune evasion still exist. Future breakthroughs will require advances in neoantigen prediction, targeted delivery, and combination therapy.

     

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