开启免疫治疗新时代：华西医院仝爱平团队系统解读癌症mRNA疫苗临床应用进展及挑战

Core Viewpoint - Cancer mRNA vaccines represent a promising new direction in cancer treatment, leveraging advancements in precision medicine and bioinformatics to enhance immune responses against tumors while addressing challenges such as tumor heterogeneity and antigen selection complexity [2][3]. Group 1: Clinical Progress and Challenges - The review summarizes the clinical progress and challenges of cancer mRNA vaccines, highlighting their ability to significantly reduce recurrence rates and induce long-term immune memory in trials for melanoma and head and neck cancers [3]. - Major obstacles include tumor heterogeneity, complex antigen selection, and vaccine stability, necessitating the integration of AI for personalized design and combination with immune checkpoint inhibitors [3][19]. Group 2: Preclinical Optimization and Development - Cancer mRNA vaccines have notable advantages, including mature synthesis technology that can encode full-length tumor antigens, enhancing T cell response efficiency without the mutation risks associated with DNA vaccines [6][8]. - Optimization efforts focus on mRNA structure (e.g., 5' cap and Poly(A) tail modifications) and delivery vehicles, with lipid nanoparticles (LNPs) being the most widely used despite challenges like hepatotoxicity [8][10]. Group 3: Mechanism of Action - The mechanism of action for mRNA cancer vaccines involves the activation of innate immune responses, where pattern recognition receptors (PRRs) identify mRNA as foreign, leading to enhanced T cell activation and immune responses against tumor cells [13][15]. Group 4: Clinical Trials and Efficacy - Ongoing clinical trials are exploring various cancer types, with mRNA vaccines encoding immune stimulators showing promise in enhancing T cell responses and improving survival rates in melanoma patients [16][18]. - Personalized neoantigen mRNA vaccines, such as Moderna's mRNA-4157, are being evaluated for their ability to significantly reduce recurrence or mortality risks in melanoma patients [17]. Group 5: Future Directions - The future of mRNA cancer vaccines is bright, with potential innovations including CARs and TCRs encoding vaccines, circRNA vaccines for sustained antigen production, and AI applications for personalized vaccine development [22][24]. - Research should focus on selecting personalized antigens, developing various immune adjuvants, and exploring the synergistic effects with gut microbiota modulation [22].