Figure 3.

Combinatorial antigen targeting for solid cancers. (A) For “OR” gate/ tandem CAR T cells the presence of one antigen is sufficient to trigger effector function, while concurrent expression of both antigens leads to synergistical improvement of activation. (B+C) “AND” gate CAR T cells require the presence of either target antigens to efficiently activate. (B) The split CAR approach taken by Kloss and colleagues uses a 1st generation CAR that recognizes antigen 1 combined with a chimeric costimulatory receptor (CCR) that provides the necessary costimulation upon encounter of antigen 2. (C) In the synthetic Notch (synNotch) approach reported by Roybal and colleagues sensing of antigen 1 by a synNotch transcriptional receptor (synNotch rec.) induces expression of a CAR that is specific for antigen 2. (D) Universal CAR T cells can target a variety of different antigens since their antigen specificity comes from the administration of soluble adaptors.