Ambrose, Christine and Su, Lihe and Wu, Lan and Dufort, Fay J. and Sanford, Thomas and Birt, Alyssa and Hackel, Benjamin J. and Hombach, Andreas and Abken, Hinrich and Lobb, Roy R. and Rennert, Paul D. (2021) Anti-CD19 CAR T cells potently redirected to kill solid tumor cells. PLOS ONE, 16 (3): e0247701. ISSN 1932-6203,
Full text not available from this repository. (Request a copy)Abstract
Successful CAR T cell therapy for the treatment of solid tumors requires exemplary CAR T cell expansion, persistence and fitness, and the ability to target tumor antigens safely. Here we address this constellation of critical attributes for successful cellular therapy by using integrated technologies that simplify development and derisk clinical translation. We have developed a CAR-CD19 T cell that secretes a CD19-anti-Her2 bridging protein. This cell therapy strategy exploits the ability of CD19-targeting CAR T cells to interact with CD19 on normal B cells to drive expansion, persistence and fitness. The secreted bridging protein potently binds to Her2-positive tumor cells, mediating CAR-CD19 T cell cytotoxicity in vitro and in vivo. Because of its short half-life, the secreted bridging protein will selectively accumulate at the site of highest antigen expression, ie. at the tumor. Bridging proteins that bind to multiple different tumor antigens have been created. Therefore, antigen-bridging CAR-CD19 T cells incorporate critical attributes for successful solid tumor cell therapy. This platform can be exploited to attack tumor antigens on any cancer.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CHIMERIC ANTIGEN RECEPTOR; B-CELLS; THERAPY; IMMUNOTHERAPY; ACTIVATION; CD19; LEUKEMIA; GLIOBLASTOMA; EXPRESSION; ANTIBODIES; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Zentren des Universitätsklinikums Regensburg > Regensburger Centrum für Interventionelle Immunologie (RCI) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 08 Sep 2022 14:25 |
| Last Modified: | 08 Sep 2022 14:25 |
| URI: | https://pred.uni-regensburg.de/id/eprint/46854 |
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