Cassatt™ DAP10/12 CARs
Progenitor Cassatt™ DAP10/12-based CARs utilize killer cell Dap10- and Dap12-signaling domains alone or in combination with traditional CD3-zeta- and Fc gamma-derived elements. DAP10 and DAP12 form hetero-tetramers that synergistically amplify signaling to cytotoxic endpoints in cytotoxic T cells and natural killer cells. This Dap10/Dap12 interaction can be exploited to improve specificity by simultaneously targeting two different antigens with co-expressed pairs of a Dap10-CAR and Dap12-CAR targeted to two different but related antigens. Subsequently, cytotoxic signaling is reduced when only one antigen is engaged but synergistically enhanced and maximal when both antigens are engaged. By requiring dual specificity recognition of target cells, Cassatt™ technology increases the stringency and specificity for activation of cytotoxic responses, enabling targeting of a broader range of tumor antigens. In addition, Cassatt™ technology can be used to target components of the tumor microenvironment.