Injectable Porous Microchips with Oxygen Reservoirs and an Immune-Niche Enhance the Efficacy of CAR T Cell Therapy in Solid Tumors

Chimeric antigen receptor (CAR) T cell therapy is a promising new class of hematological malignancy treatment. However, CAR T cells are rarely effective in solid tumor therapy mainly because of the poor trafficking of injected CAR T cells to the tumor site and their limited infiltration and survival...

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Bibliographic Details
Published in:ACS applied materials & interfaces 2020-12, Vol.12 (51), p.56712-56722
Main Authors: Luo, Zuyuan, Liu, Zhen, Liang, Zhen, Pan, Jijia, Xu, Jun, Dong, Jiebin, Bai, Yun, Deng, Hongkui, Wei, Shicheng
Format: Article
Language:English
Subjects:
Alginates - chemistry
Animals
Biological and Medical Applications of Materials and Interfaces
Drug Carriers - chemistry
Hemoglobins - chemistry
Hemoglobins - therapeutic use
Humans
Hydrogels - chemistry
Hypoxia-Inducible Factor 1, alpha Subunit - metabolism
Immunotherapy, Adoptive - methods
Interleukin-15 - chemistry
Male
Mice, Inbred BALB C
Microspheres
Neoplasms - therapy
Oxygen - metabolism
Porosity
Receptors, Chimeric Antigen - immunology
T-Lymphocytes - immunology
T-Lymphocytes - transplantation
Tumor Microenvironment - drug effects
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Summary:Chimeric antigen receptor (CAR) T cell therapy is a promising new class of hematological malignancy treatment. However, CAR T cells are rarely effective in solid tumor therapy mainly because of the poor trafficking of injected CAR T cells to the tumor site and their limited infiltration and survival in the immunosuppressive and hypoxic tumor microenvironment (TME). Here, we built an injectable immune-microchip (i-G/MC) system to intratumorally deliver CAR T cells and enhance their therapeutic efficacy in solid tumors. In the i-G/MC, oxygen carriers (Hemo) are released to disrupt the TME, and then, CAR T cells migrate from IL-15-laden i-G/MCs into the tumor stroma. The results indicate that Hemo and IL-15 synergistically enhanced CAR T cell survival and expansion under hypoxic conditions, promoting the potency and memory of CAR T cells. This i-G/MC not only serves as a cell carrier but also builds an immune-niche, enhancing the efficacy of CAR T cells.
ISSN:1944-8244
1944-8252
DOI:10.1021/acsami.0c15239