enadenotucirev-expressing FAP/CD3 bispecific FAP-TAc NG-641

An oncolytic adenoviral vector, a transgene-modified variant of enadenotucirev (EnAd), that expresses a bi-specific T-cell activator molecule FAP-TAc together with immune enhancer molecules C-X-C motif chemokine 9 (CXCL9), C-X-C motif chemokine 10 (CXCL10) and interferon alpha (IFNalpha), with potential immunomodulating and antineoplastic activities. Upon administration of NG-641, EnAd specifically infects and replicates in tumor cells and not in normal, noncancerous tissue, and selectively expresses FAP-TAc. The locally expressed FAP-TAc targets and binds to both fibroblast activating protein (FAP) on cancer associated fibroblasts (CAFs) and CD3 on T cells. This leads to T-cell activation and T-cell mediated killing of CAFs in tumor stroma. NG-641 also encodes the transgenes CXCL9, CXCL10 and IFNalpha. The production of CXCL9, CXCL10 and IFNalpha leads to the recruitment and further activation of T cells, enhancing the overall immune response and cancer cell killing. FAP, a cell surface glycoprotein, is overexpressed on tumor-associated fibroblasts but minimally expressed on normal, healthy cells.