| Autor: |
Megan K. Levings, Madeleine Speck, Nicholas A.J. Dawson, Vivian C.W. Fung, German E. Novakovsky, Emma McIver, Majid Mojibian, Qing Huang, Grace Sun, Paul C. Orban, Jana Gillies, Isaac Rosado-Sánchez |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
|
| DOI: |
10.1101/749721 |
| Popis: |
SummaryAntigen-specific regulatory T cells (Tregs) engineered with chimeric antigen receptor (CARs) are a potent immunosuppressive cellular therapy in multiple disease models. To date the majority of CAR Treg studies employed second generation CARs, encoding a CD28 or 4-1BB co-receptor signaling domain and CD3ζ, but it was not known if this CAR design was optimal for Tregs. Using an HLA-A2-specific CAR platform and human Tregs, we compared ten CARs with different co-receptor signaling domains and systematically tested their function. Tregs expressing a CAR encoding wild-type CD28 were markedly superior to all other CARs tested in anin vivomodel of graft-versus-host disease. In vitro assays revealed stable expression of Helios and ability to suppress CD80 expression on DCs as keyin vitropredictors ofin vivofunction. This comprehensive study of CAR signaling-domain variants in Tregs can be leveraged to optimize CAR design for use in antigen-specific Treg therapy. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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