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.
