autologous nectin-4/FAP-targeted CAR-T cells

A preparation of autologous T lymphocytes engineered to express a chimeric antigen receptor (CAR) specific for the tumor-associated antigen (TAA) nectin-4 and cell surface protein fibroblast activation protein (FAP), and additionally an inducible expression cassette encoding transgenic interleukin (IL) 7 (IL-7) or 12 (IL-12), with potential immunostimulating and antineoplastic activities. Upon intratumoral administration, the autologous nectin-4/FAP-targeted CAR-T cells target and bind to nectin-4-expressing tumor cells and FAP-expressing cancer associated fibroblasts (CAFs). This results in a cytotoxic T-lymphocyte (CTL) response against nectin-4-expressing tumor cells and FAP-expressing CAFs, leading to cell lysis of these cells. Upon the binding to nectin-4 and FAP and the activation of the CAR-T cells, cytokine IL-7 or IL-12 is also released. This further augments the immune responses against the tumor cells, which may include the attack of nectin-4-negative tumor cells by tumor necrosis factor alpha (TNFa). Nectin-4, a TAA belonging to the nectin family, is overexpressed in a variety of cancers, including breast, bladder, lung and pancreatic cancer. FAP, a cell surface glycoprotein, is overexpressed on CAFs but minimally expressed on normal, healthy cells.