Imugene is a clinical stage immuno-oncology company developing a range of new treatments that seek to activate the immune system of cancer patients to identify and eradicate tumors.
Clinical Pipeline
Our product pipeline includes multiple immunotherapy B-cell vaccine candidates and an oncolytic virotherapy (CF33) aimed at treating a variety of cancers in combination with standard of care drugs and emerging immunotherapies such as CAR T’s for solid tumours.
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 check here to target and eradicate solid tumours that are otherwise difficult to treat with CAR T therapy alone.
CF33
Our lead candidate is a chimeric vaccinia (pox) virus known as CF33, developed by Professor Yuman Fong, at the prestigious City of Hope Comprehensive Cancer Center in Los Angeles, California.
Vaccinia is a genetically stable double stranded DNA virus of the Poxviridae family. It has a track record of safe use in millions of humans as it was the active constituent of the vaccine that eradicated smallpox, one of the most devastating diseases known to humanity and was the first oncolytic virus demonstrating viral oncolysis in the laboratory in 1922.
Vaccinia has a short well characterised life cycle and spreads rapidly from cell to cell, but does not integrate into the host’s genome. It is highly cytolytic for a broad range of tumor cell types. It has the potential to act as both a gene therapy delivery vehicle and oncolytic agent.
CF33 is a combination of genomic sequences from multiple vaccinia virus strains to generate a new, safer and more potent virus. CF33 with the Human Sodium-Iodide Symporter (hNIS) gene, which enables imaging to track the virus in vivo and mediate targeted radiotherapy is called Vaxinia. CF33 when with hNIS and “armed” with anti PD-L1 genes, which enable enhancement of anti-cancer immunotherapy, is called CHECKVacc. We have both CF33 candidates for development.
Safety has been demonstrated in a number of pre-clinical trials and there is evidence for both a local and systemic anti-tumor response.
Through the use of CF33, we hope to improve the clinical benefits and quality of life for patients with cancers that are difficult to treat using current therapeutic approaches.