Chimeric antigen receptor (CAR)–engineered T cells (CAR T) are T cells redirected against tumors through engineered expression of CARs. These modified T cells are injected into cancer patients where they can specifically kill tumor cells. CAR T cells directed against CD19 work very well against B cell malignancies or liquid (blood) cancers, and so far, three CD-19-specific CAR T’s, namely Kymriah (Novartis), Breyanzi (BMS) and Yescarta (Gilead), have received FDA approval for the treatment of different types of B cell malignancies (blood cancers).

However, unlike in B cell malignancies, CAR T cells have shown suboptimal efficacy in solid tumors, which represent around 90% of all cancers world-wide. One of the major reasons for the limited success of CAR T in solid tumors is the lack of the selective and homogeneous expression of antigens or targets, or in layman’s terms a simple targeting point, on tumor cells. Given the ability of oncolytic viruses (OV’s) like Imugene’s CF33 OV to selectively infect cancer cells, it may be possible to selectively express a unique antigen or target from cancer cells by using an antigen/target-armed CF33 OV, followed by treatment with CAR T cells directed against that antigen or target (Figure 1).

A recent study by City of Hope scientists led by Dr. Saul Priceman demonstrated proof-of-principle for such a strategy [Park etal. 2020]. In this study, the COH team used CF33 OV to selectively deliver CD19 to tumor cells in murine cancer models, and used CAR-T cells directed against CD19. The combination of CD-19-directed CAR T with CD19-encoding OV resulted in greatly improved survival of mice compared to antigen-mismatched combinations.

The combination immunotherapy, onCARlytics, unleashes a CD19-expressing oncolytic virus CF33-CD19 to target and eradicate solid tumours that are otherwise difficult to treat with CAR T therapy alone.