Injectable and photocurable CAR-T cell formulation enhances the anti-tumor activity to melanoma in mice

被引:25
|
作者
Zhou, Weilin [1 ,2 ]
Lei, Sibei [1 ,2 ]
Liu, Mei [1 ,2 ]
Li, Dan [1 ,2 ]
Huang, Yong [1 ,2 ]
Hu, Xiaoyi [1 ,2 ,3 ]
Yang, Jinrong [1 ,2 ,4 ,5 ,6 ]
Li, Jing [1 ,2 ]
Zhang, Mengxi
Wang, Fengling [1 ,2 ]
Li, Jiaqian [1 ,2 ]
Men, Ke [1 ,2 ,7 ,8 ,9 ]
Wang, Wei [1 ,2 ,7 ,8 ,9 ]
机构
[1] Sichuan Univ, West China Hosp, Dept Biotherapy, State Key Lab Biotherapy, Chengdu, Peoples R China
[2] Sichuan Univ, West China Hosp, Canc Ctr, Chengdu, Peoples R China
[3] Sichuan Univ, Dept Gynecol & Obstet Dev & Related Dis, Women & Children Key Lab Sichuan Prov, West China Hosp 2,Key Lab Birth Defects & Related, Chengdu 610041, Peoples R China
[4] Sichuan Univ, State Key Lab Biotherapy, Dept Hematol, Hematol Res Lab, Chengdu 610041, Sichuan, Peoples R China
[5] Sichuan Univ, West China Hosp, Canc Ctr, Chengdu 610041, Sichuan, Peoples R China
[6] Sichuan Univ, West China Hosp, Canc Ctr, Dept Med Oncol, Chengdu 610041, Sichuan, Peoples R China
[7] Sichuan Univ, State Key Lab Biotherapy, Chengdu 610041, Peoples R China
[8] Sichuan Univ, West China Hosp, Canc Ctr, Chengdu 610041, Peoples R China
[9] Collaborat Innovat Ctr Biotherapy, Chengdu 610041, Peoples R China
基金
中国国家自然科学基金;
关键词
Injectable hydrogel; CAR -T therapy; Solid tumor; Immunotherapy; Controlled release; GELATIN; HYDROGELS; MEMORY; DELIVERY; IMMUNOTHERAPY; THERAPY; EXPANSION; IMMUNITY; IL-7;
D O I
10.1016/j.biomaterials.2022.121872
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
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.
引用
收藏
页数:13
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