City of Hope receives US DoD grant with upside for Imugene

A US Department of Defense Grant titled Discovery of Immune Biomarkers That Predict Response to a Novel Chimeric Immuno-Oncolytic Virus Encoding Anti-PD-L1 in Gastric Cancer Peritoneal Carcinomatosis has been awarded to prominent City of Hope researchers.

The grant US$564,173 was awarded to Yanghee Woo, MD, Associate Clinical Professor, Department of Surgery and Director, Gastroenterology Minimally Invasive Therapy Program, together with Yuman Fong, MD, Professor and Chair of the Department of Surgery.

Professor Fong is an internationally recognised expert in liver and pancreatic cancer. He has developed several surgical techniques and instruments and has also led research efforts to use genetically modified viruses to destroy cancer cells. Dr. Woo is a City of Hope surgeon-scientist specially trained and internationally recognised in robotic surgery and gastric cancer.

City of Hope is a world-renowned independent research and treatment centre for cancer, diabetes and other life-threatening diseases based near Los Angeles.

City of Hope is working closely with Australian clinical stage immuno-oncology company Imugene Limited (ASX:IMU) in the fight against cancer.

Imugene currently has a proposal on the table to license CF33 from City of Hope. The CF33 oncolytic virus (OV) technology was developed in the laboratory of Professor Fong and as we pointed out in a previous Finfeed article has been developed in two different constructs.

One version of the OV is “armed” with an immune checkpoint inhibitor inserted in the virus, which is known as CheckVacc.

The other is an unarmed construct, known as Vaxinia.

Imugene plans to conduct two separate Phase 1 clinical trials in 2020 to test a CheckVacc construct and a Vaxinia construct of the OV.

What is CF33

The CF33 Oncolytic Chimeric Poxvirus Oncolytic virotherapy (OV) utilises naturally occurring or genetically modified viruses to infect, replicate in, and kill cancer cells, while sparing healthy cells.

The first OV for human therapy was recently approved by the US Food and Drug Administration (FDA): T-VEC (talimogene laherparepvec, Amgen), for the treatment of

metastatic melanoma.

Preclinical data has demonstrated that CF33 is more efficacious than all parental viruses and some viruses in clinical trials. CF33 efficiently shrank injected tumours and distant non-injected tumours in human triple negative breast cancer, colon cancer, ovarian cancer xenograft models in mice without adverse effects at a dose that is 2-5 orders of magnitude lower than doses used for oncolytic viruses under clinical testing.

Especially impressive is that CF33 can shrink multiple types of cancer at an extremely low dose (1000 PFU). Importantly, CF33 shrinks not only injected tumours, but also non-injected distant tumours (abscopal effect). CF33 showed superior replication and cancer cell killing in NCI-60 cell lines and is more potent than all the parental and competitor viruses in most of the NCI-60 cell lines except for a few cell lines in which none of the viruses showed any effect at the low MOI (0.01).

Focus of the grant

US Department of Defense Grant focuses on the area of stomach (gastric) cancer (GC), a disease that disproportionately affects US military service members, veterans, and their beneficiaries who have increased exposure to hazardous environmental risk factors, such as H. pylori, Epstein-Barr viral infections, radiation, and tobacco smoking.

Peritoneal carcinomatosis (PC) is a fatal evolution of GC for which there is no effective treatment. Across military families and the general population, over 60% of all patients with GC will develop peritoneal disease as the most common manifestation of recurrence or metastatic presentation.

The progression of primary GC to PC is facilitated by the unique peritoneal tumor microenvironment, where metastatic peritoneal seeding requires evasion of anti-tumor immunity and maintenance of a highly immunosuppressive microenvironment.

City of Hope researchers rationalise that a combined approach using Imugene’s proposed license for novel oncolytic virus CF33 armed to express an anti-PD-L1 antibody as immune modulator could specifically kill cancer cells, convert the immunologically ‘cold’ environment of PC into a ‘hot’ environment, and enhance overall efficacy of GC therapy.

“Imugene and City of Hope are committed to help improve the length and quality of life for patients with gastric cancer. We congratulate Dr. Yanghee Woo and Dr. Yuman Fong on receiving this sizable grant. It is an honour to work with the prestigious and prolific team at City of Hope to expand the development of CF33,” Imugene’s M.D. & CEO, Ms Leslie Chong said.