肿瘤细胞治疗研究
英文原题：Vaccine therapy for pediatric high-grade glioma: current landscape, challenges, and future directions.
本综述概述了疫苗疗法用于pHGG的科学依据，详述了关键靶点，如胶质瘤相关抗原（EphA2、IL-13Rα2、survivin）、驱动突变衍生新抗原（H3.3K27M、TP53、IDH1）以及病毒抗原（CMV pp65）。我们评估了当前的疫苗平台，包括肽疫苗、树突状细胞疫苗、mRNA疫苗以及新抗原个体化方法，重点介绍了证明安全性和免疫原性的早期临床试验结果。尽管初步数据令人鼓舞，但若干挑战阻碍了临床转化，包括中枢神经系统独特的免疫环境、瘤内异质性、低突变负荷、免疫抑制性微环境、类固醇使用以及疫苗生产和试验设计中的后勤障碍。
儿童高级别胶质瘤（pHGG）是最具侵袭性的儿童脑肿瘤之一，治疗方案有限，预后较差。基于疫苗的免疫治疗提供了一种有前景的策略，通过利用肿瘤特异性或相关抗原来激发持久且毒性最小的抗肿瘤免疫应答。
BACKGROUND: Pediatric high-grade gliomas (pHGG) are among the most aggressive childhood brain tumors, with limited treatment options and poor prognosis. Vaccine-based immunotherapy offers a promising strategy by leveraging tumor-specific or associated antigens to stimulate durable anti-tumor immune responses with minimal toxicity. DISCUSSION: This review outlines the scientific rationale for vaccine therapies in pHGG, detailing key targets such as glioma-associated antigens (EphA2, IL-13Rα2, survivin), driver mutation–derived neoantigens (H3.3K27M, TP53, IDH1), and viral antigens (CMV pp65). We evaluate current vaccine platforms, including peptide vaccines, dendritic cell vaccines, mRNA-based vaccines, and neoantigen-personalized approaches, highlighting early-phase clinical trial results that demonstrate safety and immunogenicity. Despite encouraging preliminary data, several challenges hinder clinical translation, including the distinct immune environment in the central nervous system, intratumoral heterogeneity, low mutational burden, immunosuppressive microenvironments, steroid use, and logistical hurdles in vaccine production and trial design. Future research must address these barriers through optimized antigen selection, combinatorial therapies, novel delivery systems, and pediatric-specific immune profiling. CONCLUSION: With continued multidisciplinary collaboration, vaccine therapies may emerge as a meaningful addition to the therapeutic arsenal for children with pHGG.
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