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

Weilin Zhou; Sibei Lei; Mei Liu; Dan Li; Yong Huang; Xiaoyi Hu; Jinrong Yang; Jing Li; Maorong Fu; Mengxi Zhang; Fengling Wang; Jiaqian Li; Ke Men; Wei Wang

doi:10.1016/j.biomaterials.2022.121872

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

Biomaterials. 2022 Dec:291:121872. doi: 10.1016/j.biomaterials.2022.121872. Epub 2022 Oct 22.

Authors

Weilin Zhou¹, Sibei Lei¹, Mei Liu¹, Dan Li¹, Yong Huang¹, Xiaoyi Hu², Jinrong Yang³, Jing Li¹, Maorong Fu¹, Mengxi Zhang⁴, Fengling Wang¹, Jiaqian Li¹, Ke Men⁵, Wei Wang⁶

Affiliations

¹ Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, PR China.
² 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.
³ Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, PR China; Department of Hematology, Hematology Research Laboratory, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, PR China.
⁴ Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University; Chengdu, Sichuan, 610041, PR China.
⁵ Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, PR China. Electronic address: mendingbob@hotmail.com.
⁶ Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, PR China. Electronic address: weiwang@scu.edu.cn.

PMID: 36323072
DOI: 10.1016/j.biomaterials.2022.121872

Abstract

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.

Keywords: CAR-T therapy; Controlled release; Immunotherapy; Injectable hydrogel; Solid tumor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Hydrogels
Immunotherapy, Adoptive / methods
Melanoma* / therapy
Mice
Neoplasms* / therapy
Receptors, Chimeric Antigen*
T-Lymphocytes
Tumor Microenvironment

Substances

Receptors, Chimeric Antigen
gelatin methacryloyl
Hydrogels