NG-641 is an oncolytic adenoviral vector designed to deliver genes to tumor cells that produce proteins that target tumor-associated stromal fibroblasts.
The NG-641 virus encodes four separate genes:
A fibroblast activation protein (FAP)-targeting bispecific T-cell activator (FAP-TAc) to activate T-cells and decrease the tumor associated fibroblasts in tumor stroma
The chemokines CXCL9 and CXCL10 to recruit T-cells
Interferon alpha to drive dendritic cell priming and further activate T-cells
Stromal fibroblasts are believed to protect and nourish tumors, supporting tumor growth and driving tumor immunosuppression. Patients with stroma rich tumors have been shown to have poorer prognoses than patients with low levels of tumor stroma. At PsiOxus, we developed NG-641 to eradicate tumor-associated stromal fibroblasts in order to reduce tumor growth and stimulate anti-cancer immune responses, even in tumors poorly infiltrated by immune cells.
NG-641 combines a bi-specific FAP-targeted T-cell activator to activate T-cells to kill fibroblasts, plus three additional genes to further recruit and activate those T-cells (Figure 1.) NG-641 is designed to be administered intravenously and infect and replicate in tumor cells. Upon replication, those same tumor cells are simultaneously directed by the encoded genes to produce the four therapeutics in NG-641 locally to mount an immune attack on the fibroblasts in the tumor stroma to enable subsequent immune-mediated destruction of cancer cells. (Figure 1.)
NG-641 is in preclinical development and PsiOxus intends to seek an Investigation New Drug approval and to start a Phase 1 clinical trial in 2019.
View the SITC 2018 poster on NG-641 here.
View the Fap-Tac Publication in EMBO Mol Med. here.