Figure 1.

CAR T cell antigen-targeting strategies and pancreatic cancer TME. (A) The pancreatic TME consists of tumor cells as well as many immunosuppressive cells, such as CAFs, TAMs, MDSCs, PSCs, and Treg cells. (B) CAR T cells can be directed to the TAA expressed on pancreatic cancer cells and/or other antigens targeting the TME components, such as FAP on CAFs. (C) CARs are composed of extracellular, transmemebrane and endo-domains. The extracellular domain consists of an antibody variable heavy chain (VH) and a light chain (VL) domain, which are derived from an scFv from an antibody specific for a TAA. A flexible hinge region links the extracellular domain to a transmembrane and endodomain. The endodomain has cytoplasmic signaling regions derived from CD3ζ and costimulatory signaling domains. TAMs, tumor-associated macrophages; CAFs, cancer associated fibroblasts; MDSCs, myeloid-derived suppressor cells; Tregs, regulatory T cells; PSCs, pancreatic stellate cells; FAP, fibroblast activation protein; scFv, single chain variable fragment. TAA, tumor associated antigen; TME, tumor microenvironment.