Zhou Weilin, Lei Sibei, Liu Mei, Li Dan, Huang Yong, Hu Xiaoyi, Yang Jinrong, Li Jing, Fu Maorong, Zhang Mengxi, Wang Fengling, Li Jiaqian, Men Ke, Wang Wei
Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, PR China.
Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, PR China; Department of Gynecology and Obstetrics, Development and Related Disease of Women and Children Key Laboratory of Sichuan Province, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second Hospital, Sichuan University, Chengdu, 610041, PR China.
Biomaterials. 2022 Dec;291:121872. doi: 10.1016/j.biomaterials.2022.121872. Epub 2022 Oct 22.
The chimeric antigen receptor-T cells (CAR-T) therapy, as a novel personalized immunotherapy, has shown prominent clinical efficacy in the treatment of B-cell malignancies. However, the progress in solid tumors was hindered by multiple elements in the tumor immunosuppressive microenvironment. In this study, an injectable and photocurable Gelatin Methacryloyl (GelMA) hydrogel was applied to be a depot of CAR-T cells, thus forming an injectable CAR-T Gelatin Methacryloyl hydrogels Delivery (i-GMD) system. According to our results, CAR-T cells in this system could be normally amplified, sustained released, and play an anti-tumor role in vitro. When compared with local or intravenously injection of CAR-T solution, injection of i-GMD matrix around tumor demonstrated enhanced anti-tumor effect and markedly extended survival of mice. Our research outcomes indicated that this therapeutic strategy might hopefully provide a treatment for patients with unresectable tumors.
嵌合抗原受体T细胞（CAR-T）疗法作为一种新型的个性化免疫疗法，在治疗B细胞恶性肿瘤方面已显示出显著的临床疗效。然而，实体瘤治疗的进展受到肿瘤免疫抑制微环境中多种因素的阻碍。在本研究中，一种可注射且可光固化的甲基丙烯酸明胶（GelMA）水凝胶被用作CAR-T细胞的储存库，从而形成一种可注射的CAR-T甲基丙烯酸明胶水凝胶递送（i-GMD）系统。根据我们的结果，该系统中的CAR-T细胞能够正常扩增、持续释放，并在体外发挥抗肿瘤作用。与局部或静脉注射CAR-T溶液相比，在肿瘤周围注射i-GMD基质显示出增强的抗肿瘤效果，并显著延长了小鼠的生存期。我们的研究结果表明，这种治疗策略有望为不可切除肿瘤患者提供一种治疗方法。
