Journal
SCIENCE ADVANCES
Volume 8, Issue 14, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abn8264
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Funding
- Bill and Melinda Gates Foundation [OPP1113682]
- American Cancer Society [RSG-18-133-01]
- NSF Graduate Research Fellowships
- Stanford Graduate Fellowship in Science and Engineering
- Siebel Scholarship
- National Cancer Institute of the NIH [F32CA247352]
- NSERC Postgraduate Scholarship
- Stanford BioX Bowes Graduate Student Fellowship
- NIH Cell and Molecular Biology Training Program [T32 GM007276]
- Eastman Kodak Fellowship
- Schmidt Science Fellows program
- Rhodes Trust
- NIH National Cancer Institute Grant [R37 CA214136]
- NIH F31 [1F31CA250405-01]
- Center for Human Systems Immunology
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This study introduces a simple-to-implement injectable hydrogel for controlled co-delivery of CAR-T cells and stimulatory cytokines to improve treatment of solid tumors. The unique architecture of this material inhibits passive diffusion of entrapped cytokines and allows active motility of entrapped cells for long-term retention, viability, and activation of CAR-T cells. The transient inflammatory niche generated following administration leads to sustained exposure of CAR-T cells, induction of tumor-reactive CAR-T phenotype, and enhanced treatment efficacy.
Adoptive cell therapy (ACT) has proven to be highly effective in treating blood cancers, but traditional approaches to ACT are poorly effective in treating solid tumors observed clinically. Novel delivery methods for therapeutic cells have shown promise for treatment of solid tumors when compared with standard intravenous administration methods, but the few reported approaches leverage biomaterials that are complex to manufacture and have primarily demonstrated applicability following tumor resection or in immune-privileged tissues. Here, we engineer simple-to-implement injectable hydrogels for the controlled co-delivery of CAR-T cells and stimulatory cytokines that improve treatment of solid tumors. The unique architecture of this material simultaneously inhibits passive diffusion of entrapped cytokines and permits active motility of entrapped cells to enable long-term retention, viability, and activation of CAR-T cells. The generation of a transient inflammatory niche following administration affords sustained exposure of CAR-T cells, induces a tumor-reactive CAR-T phenotype, and improves efficacy of treatment.
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