On May 2, 2018 EpicentRx, a San Diego biotechnology company developing a next-generation immunotherapy platform of viruses that infect and kill cancer cells for the treatment of several tumor types, reported that it has developed the first ever series of oncolytic viruses tailored to tumors of individual patients (Press release, EpicentRx, MAY 2, 2018, View Source [SID1234528889]). The first patient, treated at the University of Cincinnati (UC) in Cincinnati, Ohio, by John Morris, MD, professor at the UC College of Medicine and director of the area’s only Phase I/Experimental Therapeutics Program, has been enrolled to receive a personalized virus that has been "armed" with peptide fragments or neoantigens from his specific tumors.
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Neoantigens are ideal targets for the immune system because they are selectively expressed on tumors not on normal cells. Viruses naturally target and kill cancer cells and these personalized viruses, which are derived from viruses that cause the common cold, have been engineered to improve on that ability since they use the machinery of the cancer cell to produce thousands of copies of themselves and the neoantigens that they are carrying. Hence, these viruses are administered with the goal of training the immune system to seek out and destroy the cancer cells that display these neoantigens.
This trial "provides proof-of-principle that personalized viral vaccines tailored and targeted to patient tumors can be made quickly and on demand," said Dr. Tony R. Reid, Chief Scientific Officer of EpicentRx and Associate Professor of Oncology at UCSD in California.
Dr. Corey A. Carter, CEO of EpicentRx, added that while current treatment paradigm in oncology relies on off the shelf, one size fits all therapies, "we know that every patient and patient’s tumor is different. To target an individual tumor in individual patients is nothing short of a revolution."
Drs. Carter and Reid felt that further development of personalized viral vaccines is warranted in combination with other immunotherapy weapons such as checkpoint inhibitors, which also trigger immune responses against cancer neoantigens, albeit non-specifically. "The reality is that other immunotherapies, such as checkpoint inhibitor drugs, only benefit 20-25% of patients in selected tumor types. There’s nothing for the other 75-80% of patients that don’t benefit. We can and must do better. These viruses are potentially a way to increase response rates so that the other 75-80% of patients start to benefit," said Dr. Carter.
"No two cancer cells are exactly alike, making it difficult to target cancer cells with drugs that inhibit one receptor or even one pathway since the cancer cells may and often do vary with respect to genetic changes and survival mechanisms," says Dr. Morris. "This personalized viral vaccine has the ability to contain express many different neoantigens from the tumor, targeting multiple genetic mutations in tumor cells, which could potentially prevent the cancer cells from sidestepping the immune system. We are excited to be part of this trial, which could prove beneficial for many patients."
"When you infect a cancer cell with a virus, it is like waving a big red flag at a bull, which stimulates the immune system to ‘go after’ the cancer. But like a matador cancer often has the ability to maneuver away from the threatening attack. In our experiments we have found that when the virus is personalized to the tumor with multiple neoantigens, the tumor is unable to escape the immune system’s charge and is ‘gored’," said Dr. Reid. "Effectively what we are doing with these viruses is to use the immune system’s natural ability to attack many target antigens, which is what happens every time we get an infection."
Oncolytic viruses have been tested in thousands of patients in the clinic and generally appear to only cause flu-like symptoms for about a week, according to Dr. Reid.
The viruses were manufactured in house according to Good Manufacturing Practice (GMP) regulations and samples of patient tumors and normal DNA from blood underwent whole-exome sequencing to reveal mutations present only in the tumor.
According to Dr. Carter, "Future personalized viral vaccine trials will be done under a separate Investigational New Drug application to the FDA, so many more patients with advanced disease may be enrolled to test the efficacy of the viruses both alone and with checkpoint blockade and other immunotherapeutics. Personalized viruses have the potential to be applied to any cancer with enough neoantigens for vaccination."
Tumor-targeting viruses can rally the immune system against cancers, boosting the efficacy of immunotherapy drugs and opening the door to promising combination treatments for aggressive and difficult-to-treat cancers. Many viruses naturally target and kill cancer cells, and experimental oncolytic viruses are often engineered to improve that ability.