Enhanced CAR-T cell activity against solid tumors by vaccine boosting through the chimeric receptor
| Autor: | Wuhbet Abraham, Naveen K. Mehta, Murillo Silva, Simon Liang, Jason Y. Chang, Michael Fichter, Darrell J. Irvine, Nikki Thai, Leyuan Ma, K. Dane Wittrup, Benjamin J. Cossette, Chensu Wang, Tanmay Dichwalkar, Daniel Garafola, Na Li, Sudha Kumari, Angela Q. Zhang |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Vaccines Multidisciplinary Chemistry medicine.medical_treatment Cell HEK 293 cells Priming (immunology) Immunotherapy Chimeric antigen receptor Article 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Antigen 030220 oncology & carcinogenesis Neoplasms medicine Cancer research Humans Receptor Lymph node human activities |
| Popis: | Chimeric antigen receptor-T cell (CAR-T) therapy has been effective in the treatment of hematologic malignancies, but it has shown limited efficacy against solid tumors. Here we demonstrate an approach to enhancing CAR-T function in solid tumors by directly vaccine-boosting donor cells through their chimeric receptor in vivo. We designed amphiphile CAR-T ligands (amph-ligands) that, upon injection, trafficked to lymph nodes and decorated the surfaces of antigen-presenting cells, thereby priming CAR-Ts in the native lymph node microenvironment. Amph-ligand boosting triggered massive CAR-T expansion, increased donor cell polyfunctionality, and enhanced antitumor efficacy in multiple immunocompetent mouse tumor models. We demonstrate two approaches to generalizing this strategy to any chimeric antigen receptor, enabling this simple non-human leukocyte antigen-restricted approach to enhanced CAR-T functionality to be applied to existing CAR-T designs. |
| Databáze: | OpenAIRE |
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