Lots of good posts here on various topics. I guess I wouldn't...

Lots of good posts here on various topics. I guess I wouldn't mind throwing my thoughts into this thread...

Vaxinia - potency sets it apart from traditional oncolytic viruses

I think it is important when discussing oncolytic viruses and their potential efficacy, given what has taken place in the past, to understand that Vaxinia is a much more potent strain of oncolytic virus than either traditional oncolytic viruses, or indeed the initial strains of CF33. It is worthwhile noting, as medicalnewstoday.com did back in 2022 that laboratory studies suggest Vaxinia may be more effective than the previous generation of oncolytic viruses in reducing the size of tumors, making this therapy especially promising. At the time Dr. Yuman Fong, the chair of the Department of Surgery at City of Hope, told Medical News Today, “The particular importance of CF33/ Vaxinia is that this virus is designed to target all types of cancers. It is one of the first of a new generation of therapeutic viruses that would be much more potent than prior viruses, and it is potentially more selective for cancer while able to spare normal tissues.”

City of Hope - developing strategies to target solid tumours utilising oncolytic viruses

Much is made of targeted and precision therapy on this thread. Historically speaking targeted or precision medicine has borne the most fruit when it comes to cancer therapies. Hence the reason City of Hope devoted much time in researching strategies to selectively target solid tumours, as opposed to simply performing the standard IT route, which as Mason points out may or may not be successful. The City of Hope as we now know adopted the strategy of utilising an oncolytic virus to prime the tumor cells for destruction by eliciting CD19, which serves as a target for the CAR T-cell therapy. At the time Robert J. Hariri, MD, PhD, founder, chairperson, and chief executive officer of Celularity, Inc. stated in a press release. “Most solid tumors have variable targetable antigens, limiting CAR T-cell therapy efficacy. This treatment strategy with Imugene has the potential to apply to a new range of indications by enabling CD19-targeted cellular medicine to expand from its current effective usage in CD19-positive lymphomas and leukemia and potentially become applicable to a variety of solid tumors through inducing uniform expression of CD19 in solid tumors.” The licensing and development of such a strategy, referred to by Imugene as Oncarlytics, is sure to excite all those encouraged by a targeted approach to cancer therapy.

Combining with RenovoRx to target and treat difficult to access tumours

Professor Fong has even taken targeting solid tumours with CF33 a step further by aligning with RenovoRx (NASDAQ:RNXT) who recently presented new positive data on progression-free survival from the pivotal Phase 3 open label TIGeR-PaC study of RenovoGem (intra-arterial administration of gemcitabine) in locally advanced pancreatic cancer. As part of the collaboration, Imugene and RenovoRx will investigate the ability to administer Imugene’s CF33 oncolytic virus technology with RenovoRx’s TAMP therapy platform. The ability to treat difficult-to-access tumours, such as pancreatic and liver cancers, by delivering CF33 trans-arterially may be valuable to cancer patients compared to traditional administration methods where dense fibrous tissue and lack of blood vessels supplying the tumours have been shown to limit therapy uptake.

Adding Keytruda to the Vaxinia mix

One of Masons recent posts alluded to the success of Keytruda in treating solid tumours, along with from memory chemotherapy. The current Vaxinia (MAST) Trial has sought fit to add Keytruda to the Vaxinia mix, given the MAB’s efficacy in this treatment area. It is hoped this combination may increase the quantity of pdl1 protein in cancer cells, making them more susceptible to immunotherapy approaches. Its worth noting though, as Mason does, that while oncolytic viruses have repeatedly killed cancer cells in preclinical studies, few have sufficiently stimulated the immune system enough to warrant FDA Approval. Hence its going to be interesting to visualise on April 9 whether Vaxinia, or indeed Vaxinia in combination with pembroluzimab, has continued to produce positive immune responses in those being treated, as announced in early November 2023.

Dosage rates may hold the key

Despite Vaxinia being a potent brew, the constraints imposed by the FDA on Imugene’s current MAST Trial, have meant it is a slow boat to China when it comes to weaving ones way through the dosage restraints imposed on the oncolytic virus. Therefore I wouldn’t read too much into early results of Check Vacc, as Mason appears to be doing. The therapeutic window when it comes to the administration of Vaxinia to solid tumour patients, may well allow for doses of 10 parts to the 9, which is hundreds of thousands times stronger than the initial clinical trial dosage rates administered to patients. We are yet to see the results of Vaxinia when dosed at 10 parts to the 8, a dosage escalation level that may hold the key to the oncolytic viruses efficacy.

In the future such extraneous measures in dose escalation trials may not be required, at least if machine learning and Artificial Intelligence (AI) have anything to do with it. One member of Professor Fongs team at the City of Hope Richard Li has been working with machine learning, and more recently Artificial Intelligence (AI) , to empirically characterise dosimetric predictors of toxicity in patients treated as part of a prospective clinical trial. See https://www.researchgate.net/publication/372100522_Explainable_Artificial_Intelligence_to_Identify_Dosimetric_Predictors_of_Toxicity_in_Patients_with_Locally_Advanced_Non_Small_Cell_Lung_Cancer_A_Secondary_Analysis_of_RTOG_0617 for more

What’s next for Professor Fong?

With the current Vaxinia Trial coming to a close my mind turns to what may be next on the agenda for the esteemed surgeon and medical researcher, Professor Yuman Fong. Having been actively involved in progressing Vaxinia with the FDA and Imugene, I'd be confident in assuming when all is said and done, if Vaxinia achieves Registration Trial Approval, there may be some other lights shining on his horizon.
During lunch in late 2022 with YF and SP we were discussing the prospective efficacy of Vaxinia, Oncarlytics potential and the combination of both, when the conversation turned to preventative medicine, a passion of Professor Fong's. If one day he is successful in eradicating multiple solid tumour indications I’m confident early diagnosis of cancer and preventative medicine are sure to be on his bucket list of things to do before he approaches retirement. City of Hope already offer lifesaving cancer prevention and early detection for thousands of families at risk for inherited cancers by providing a full picture of genomic information. As City of Hope’s website notes

When a patient is found to carry a gene that increases susceptibility to cancer, such as a BRCA1 mutation, the Center for Precision Medicine also makes genomic testing available to their family members. For those at heightened risk for cancer, there's the chance to undergo screenings for early detection. Some may even be able to reduce that risk with medications or preventive surgeries.Other family members may learn that they do not carry a cancer-susceptibility gene. This, too, is a favourable outcome, sparing those at average risk from unnecessary screenings.

With all this in mind I was excited to see City of Hope announcing a few weeks back they were taking leading-edge clinical screening and care into Southern California communities and beyond with the launch of their new mobile cancer prevention and screening program. The program, the first in the U.S. to provide this level of mobile comprehensive cancer prevention and screening services, marks an important advancement in City of Hope’s long-standing mission to bridge health equity gaps and address community health needs.

City of Hope’s highly advanced mobile clinic assesses the risk and screens for at least 15 different types of cancer - photo courtesy of the LA Times

“Our comprehensive mobile cancer prevention and screening program is the next step in our mission to expand access to optimal cancer care, bringing our expertise outside the walls of our campus and into the communities we serve,” said Harlan Levine, president of Health Innovation and Policy at City of Hope. “We know that identifying and addressing cancers early saves lives, and we want to do our part to ensure every person has access to these services and help create a healthier, more equitable future for all.” See LA Times for more


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