Novel adapter CAR-T cell technology for precisely controllable multiplex cancer targeting
oleh: Christian M. Seitz, Joerg Mittelstaet, Daniel Atar, Jana Hau, Selina Reiter, Clara Illi, Verena Kieble, Fabian Engert, Britta Drees, Giulia Bender, Ann-Christin Krahl, Philipp Knopf, Sarah Schroeder, Nikolas Paulsen, Alexander Rokhvarguer, Sophia Scheuermann, Elena Rapp, Anna-Sophia Mast, Armin Rabsteyn, Sabine Schleicher, Stefan Grote, Karin Schilbach, Manfred Kneilling, Bernd Pichler, Dominik Lock, Bettina Kotter, Sandra Dapa, Stefan Miltenyi, Andrew Kaiser, Peter Lang, Rupert Handgretinger, Patrick Schlegel
| Format: | Article |
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| Diterbitkan: | Taylor & Francis Group 2021-01-01 |
Deskripsi
Chimeric antigen receptor (CAR)-T therapy holds great promise to sustainably improve cancer treatment. However, currently, a broad applicability of CAR-T cell therapies is hampered by limited CAR-T cell versatility and tractability and the lack of exclusive target antigens to discriminate cancerous from healthy tissues. To achieve temporal and qualitative control on CAR-T function, we engineered the Adapter CAR (AdCAR) system. AdCAR-T are redirected to surface antigens via biotin-labeled adapter molecules in the context of a specific linker structure, referred to as Linker-Label-Epitope. AdCAR-T execute highly specific and controllable effector function against a multiplicity of target antigens. In mice, AdCAR-T durably eliminate aggressive lymphoma. Importantly, AdCAR-T might prevent antigen evasion by combinatorial simultaneous or sequential targeting of multiple antigens and are capable to identify and differentially lyse cancer cells by integration of adapter molecule-mediated signals based on multiplex antigen expression profiles. In consequence the AdCAR technology enables controllable, flexible, combinatorial, and selective targeting.