Made in City of Hope: Cancer vaccine with a two-pronged approach

October 24, 2014 | by City of Hope

Although chemotherapy can be effective in treating cancer, it can also exact a heavy toll on a patient’s health. One impressive alternative researchers have found is in the form of a vaccine. A type of immunotherapy, one part of the vaccine primes the body to react strongly against a tumor; the second part directly attacks the tumor itself. This double-pronged approach could be both more powerful against cancer and far less toxic to the body than traditional chemotherapy.

Don Dimond, Ph.D. and Vincent Chung, M.D. City of Hope researchers Don Diamond, left, and Vincent Chung have developed a cancer vaccine and are now testing its effectiveness in clinical trials.

A partnership

Don J. Diamond, Ph.D., director of the Division of Translational Vaccine Research, developed the anti-cancer vaccine in his lab with former colleague Joshua D.I. Ellenhorn, M.D. The vaccine consists of two parts: a vector, or carrier, virus, and an active agent that does the work. The carrier is a well-known, modified smallpox virus often used in research. The active agent — the real powerhouse in the vaccine — is the gene p53. Normally, p53 suppresses tumor growth. But in many cancer patients, the gene is mutated, allowing cancers to grow. The vaccine is designed to deliver normal, nonmutated versions of the gene to the body.

Studies in mice showed that the vaccine worked. That is, it improved general immune response and fought existing tumors. Human trials were needed. For that, Diamond partnered with Vincent Chung, M.D., a City of Hope oncologist who specializes in phase I trials. Those studies are conducted among small groups of participants to test the safety, dosage and side effects of new therapies.

A breakthrough

The vaccine was given to 12 patients whose advanced metastatic colon, gastric or pancreatic cancers had been resistant to treatment. The study found that, as in the preclinical trial, the vaccine created slight, flu-like symptoms indicating an immune response. It also proved to be extremely safe in both low doses and high doses. Additional studies will determine the most effective dose of the vaccine.

It could only happen here

City of Hope specializes in collaborations that turn discoveries into realities. Chung even organizes an annual phase I retreat, enabling City of Hope’s doctors and scientists to present their work to each other and build new projects together.

Access to on-site manufacturing facilities saved time and money, allowing Diamond and Chung to quickly move the vaccine from preclinical to human trials. Rather than looking for a company to manufacture their vaccine, City of Hope did it on-site in its Food and Drug Administration (FDA)-compliant Center for Biomedicine & Genetics.

Although federal funding to make vaccines is difficult to obtain, City of Hope has provided funds for a new lot of the vaccine, which also will be produced on campus.

Moving forward

A phase II trial, to test the vaccine’s effectiveness, is now being planned. With safety and dosage established, the vaccine can be given to patients with less-advanced cancers. This will provide more insight into how the body reacts to, and fights, cancer.

To increase the body’s response to the vaccine, researchers will combine it with new groundbreaking antibody therapies recently approved by the FDA. The research that led the way for translating these antibodies for human use was developed in the early ‘80s at City of Hope by Arthur Riggs, Ph.D., chair, Department of Diabetes and Metabolic Diseases Research, and then postdoctoral fellow, Shmuel Cabilly, Ph.D. Ultimately this may offer many cancer patients the chemotherapy alternative they desperately need.

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