肿瘤细胞治疗研究
英文原题：Immunotherapy approaches for the treatment of diffuse midline gliomas.
中位总生存期不足 12 个月，诊断后 2 年死亡率为 90%。
弥漫性中线胶质瘤（DMG）是一组高度侵袭性、几乎均致死的儿童肿瘤，导致多数儿童脑肿瘤相关死亡。患者中位总生存期不足12个月，确诊后2年死亡率达90%。对肿瘤生物学机制的研究和大量临床试验，仍未能显著改善其极差预后。持续开发新型有效治疗方案，是DMG领域亟待推进的重要工作。由于DMG无法通过手术切除、对放疗仅有有限应答，且对传统化疗耐药，免疫治疗已成为有前景的替代疗法。本文总结DMG的多种免疫治疗及其特定局限，包括细胞疗法、溶瘤病毒疗法或免疫病毒疗法、免疫检查点抑制以及免疫调节性疫苗策略；并重点介绍抗GD2 CAR-T治疗弥漫性内生型脑桥胶质瘤（DIPG）患者近期取得的临床成功。最后，本文讨论如何将临床前研究和早期临床试验数据转化为DMG患者有效、标准化治疗所面临的挑战。
Diffuse midline gliomas (DMG) are a highly aggressive and universally fatal subgroup of pediatric tumors responsible for the majority of childhood brain tumor deaths. Median overall survival is less than 12 months with a 90% mortality rate at 2 years from diagnosis. Research into the underlying tumor biology and numerous clinical trials have done little to change the invariably poor prognosis. Continued development of novel, efficacious therapeutic options for DMGs remains a critically important area of active investigation. Given that DMGs are not amenable to surgical resection, have only limited response to radiation, and are refractory to traditional chemotherapy, immunotherapy has emerged as a promising alternative treatment modality. This review summarizes the various immunotherapy-based treatments for DMG as well as their specific limitations. We explore the use of cell-based therapies, oncolytic virotherapy or immunovirotherapy, immune checkpoint inhibition, and immunomodulatory vaccination strategies, and highlight the recent clinical success of anti-GD2 CAR-T therapy in diffuse intrinsic pontine glioma (DIPG) patients. Finally, we address the challenges faced in translating preclinical and early phase clinical trial data into effective standardized treatment for DMG patients.
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