Qin Deguang, Huang Wenyong, Shen Dengke, Chong Longyi, Yang Zeyu, Wei Boyang, Li Xifeng, Li Ran, Liu Wenchao
Department of Neurosurgery, Huangpu People's Hospital of Zhongshan, Zhongshan, China.
Neurosurgery Center, Department of Cerebrovascular Surgery, The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Sci Technol Adv Mater. 2024 Nov 7;25(1):2426444. doi: 10.1080/14686996.2024.2426444. eCollection 2024.
Glioma is the most common primary malignant tumor of the central nervous system in adults. Although immunotherapy, especially tumor vaccines, has made some progress in the treatment of gliomas compared with surgery and radiotherapy. However, the lack of specific or relevant tumor antigens severely limits the further development of tumor vaccines. Here, we report a bio-derived vaccine (TMV@CpG) derived from glioma cell membrane vesicles and carrying TLR9 agonist CpG as adjuvant, which was loaded onto the GelMA microneedle to obtain the microneedle vaccine (MN-TMV@CpG). Microneedle vaccine fully utilize the innate immune cells rich in the skin, inducing stronger cellular immune responses. In subcutaneous tumor models, MN-TMV@CpG reversed the immune-suppressing microenvironment of tumor, and effectively inhibited tumor progression. In an intracranial tumor model, MN-TMV@CpG significantly prolonged the survival duration and induced stronger immune memory responses in tumor bearing mice when combined with anti-PD1 mAb. These results suggest that bio-derived nanovaccines can be used as a potential antitumor immunotherapy strategy.
胶质瘤是成人中枢神经系统最常见的原发性恶性肿瘤。尽管免疫疗法，尤其是肿瘤疫苗，与手术和放疗相比，在胶质瘤治疗方面取得了一些进展。然而，缺乏特异性或相关肿瘤抗原严重限制了肿瘤疫苗的进一步发展。在此，我们报告一种源自胶质瘤细胞膜囊泡并携带TLR9激动剂CpG作为佐剂的生物衍生疫苗（TMV@CpG），其被加载到甲基丙烯酰化明胶微针上以获得微针疫苗（MN-TMV@CpG）。微针疫苗充分利用皮肤中丰富的先天免疫细胞，诱导更强的细胞免疫反应。在皮下肿瘤模型中，MN-TMV@CpG逆转了肿瘤的免疫抑制微环境，并有效抑制肿瘤进展。在颅内肿瘤模型中，MN-TMV@CpG与抗PD1单克隆抗体联合使用时，显著延长了荷瘤小鼠的生存时间，并诱导了更强的免疫记忆反应。这些结果表明，生物衍生纳米疫苗可作为一种潜在的抗肿瘤免疫治疗策略。
