Novel adapter CAR-T cell technology for precisely controllable multiplex cancer targeting

Oncoimmunology. 2021 Dec 2;10(1):2003532. doi: 10.1080/2162402X.2021.2003532. eCollection 2021.


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.

Keywords: CAR-T cell; Immunotherapy; adapter CAR-T cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Immunotherapy, Adoptive
  • Mice
  • Neoplasms* / therapy
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Chimeric Antigen* / genetics
  • T-Lymphocytes
  • Technology


  • Receptors, Antigen, T-Cell
  • Receptors, Chimeric Antigen

Grants and funding

The authors acknowledge financial support by the Deutsche Forschungsgemeinschaft (DFG) - German Research Foundation [Projektnummer 411791562] to Patrick Schlegel and Christian M. Seitz. The authors thank Stephanie Zug, Dennis Haupt and Petra Lehnert for excellent technical assistance.The work was done at the University Children’s Hospital and in the Department of Preclinical Imaging and Radiopharmacy at the University of Tuebingen, Germany as well as at Miltenyi Biotec Bergisch-Gladbach, Germany.