BOKU - Universität für Bodenkultur Wien - Forschungsinformationssystem

Gewählte Publikation:

Salzer, B; Schueller, CM; Zajc, CU; Peters, T; Schoeber, MA; Kovacic, B; Buri, MC; Lobner, E; Dushek, O; Huppa, JB; Obinger, C; Putz, EM; Holter, W; Traxlmayr, MW; Lehner, M.
(2020): Engineering AvidCARs for combinatorial antigen recognition and reversible control of CAR function
NAT COMMUN. 2020; 11(1), 4166 FullText FullText_BOKU

T cells engineered to express chimeric antigen receptors (CAR-T cells) have shown impressive clinical efficacy in the treatment of B cell malignancies. However, the development of CAR-T cell therapies for solid tumors is hampered by the lack of truly tumor-specific antigens and poor control over T cell activity. Here we present an avidity-controlled CAR (AvidCAR) platform with inducible and logic control functions. The key is the combination of (i) an improved CAR design which enables controlled CAR dimerization and (ii) a significant reduction of antigen-binding affinities to introduce dependence on bivalent interaction, i.e. avidity. The potential and versatility of the AvidCAR platform is exemplified by designing ON-switch CARs, which can be regulated with a clinically applied drug, and AND-gate CARs specifically recognizing combinations of two antigens. Thus, we expect that AvidCARs will be a highly valuable platform for the development of controllable CAR therapies with improved tumor specificity. The lack of tumour-specific antigens and control over T-cell activity limits the development of CAR-T cell therapies for solid tumours. Here the authors present an avidity-controlled CAR platform with inducible logic control functions.
Autor/innen der BOKU Wien:
Lobner Elisabeth
Obinger Christian
Traxlmayr Michael
Zajc Charlotte
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