Publications Repository - Helmholtz-Zentrum Dresden-Rossendorf

Versatile chimeric antigen receptor platform for controllable and combinatorial T cell therapy

Feldmann, A.; Hoffmann, A.; Bergmann, R.; Koristka, S.; Berndt, N.; Arndt, C.; Loureiro, L. R.; Kittel-Boselli, E.; Mitwasi, N.; Kegler, A.; Lamprecht, C.; González Soto, K. E.; Bachmann, M.

Chimeric antigen receptor (CAR) T cells show remarkable therapeutic effects in some hematological malignancies. However, CAR T cells can also cause life-threatening side effects. In order to minimize off-target and on-target/off-tumor reactions, improve safety, enable controllability, provide high flexibility, and increase tumor specificity, we established a novel humanized artificial receptor platform termed RevCARs. RevCAR genes encode for small surface receptors lacking any antigen-binding moiety. Steering of RevCAR T cells occurs via bispecific targeting molecules (TMs). The small size of RevCAR-encoding genes allows the construction of polycistronic vectors. Here, we demonstrate that RevCAR T cells efficiently kill tumor cells, can be steered by TMs, flexibly redirected against multiple targets and used for combinatorial targeting following the “OR” and “AND” gate logic.

Keywords: Chimeric antigen receptor (CAR); T cell therapy; tumor immunotherapy; adaptor CAR platform; combinatorial gated targeting

Publ.-Id: 31204