June 3, 2013 | by Tami Dennis
If doubts remained about immunotherapy’s potential as a cancer fighter, a new study should help ease them.
City of Hope researchers administered a vaccine known as MVA-p53 to 11 patients with metastatic colon, gastric or pancreas cancer whom standard treatments had failed to help. Each received three different doses of the vaccine, designed to prompt the immune system to fight cancer.
In announcing the results of their first-in-human trials, City of Hope researchers report that their vaccine is well-tolerated – in other words, it’s safe. None were cured, but for phase 1 trials, that isn’t the goal.
“Considering the advanced disease and pretreatment with chemotherapy that is the requirement to enter the trial, we were not anticipating major responses,” said Don Diamond, Ph.D., the Tim Nesvig Lymphoma Research Fellow at City of Hope and one of the study authors. “However, the completion of this trial sets up a series of new proposals to enhance the efficacy of the vaccine.” The vaccine is based on a pox virus called MVA, often used in research and by the government as a preventive vaccine against smallpox. Here, the virus was simply used as a vector, meaning it carried the agent – in this case a gene – that did the actual work. The gene was an unmutated form of the tumor suppressor p53. (For details, see Project 4 on this page.)
Cancer patients, and some healthy adults, have an immune response to p53 – meaning it stimulates specific T cells. Researchers hope that by expanding such cells, they’ll be able to stabilize tumors, even shrink them.
Among the options the City of Hope team is now considering is partnering the vaccine with a novel class of agents referred to as checkpoint inhibitors, which have the potential to sensitize tumors to anti-cancer agents.
They also want to test the vaccine further. “Expansion of the patient population, now that we know it is safe, will be sought,” said Diamond, director of the Division of Translational Vaccine Research. “This includes [patients with] other adenocarcinomas such as ovarian, lung and breast.”
In addition, the researchers will seek the Food and Drug Administration’s approval to administer the vaccine to patients with less advanced disease. Already, the vaccine has been shown to protect mice from cancers of the breast, colon and pancreas.
Results of the phase 1 trial are being presented at the American Society of Clinical Society’s annual meeting in Chicago. The principal investigator and lead author was Vincent M. Chung, assistant professor in the Department of Medical Oncology & Therapeutics Research at City of Hope.
Other authors were Nicola Hardwick, Ph.D.; Joshua D.I. Ellenhorn, M.D.; Jonathan R. Espenschied; Dean Lim, M.D.; Peiguo Chu, M.D.; Ph.D.; Dajun Qian, Ph.D.; Joseph Kim, M.D.; Joseph Chao, M.D.; Marwan Fakih, M.D.; Yun Yen, M.D., Ph.D., the Dr. & Mrs. Allen Y. Chao Chair in Developmental Cancer Therapeutics; and Diamond.
The research was supported by the National Cancer Institute of the National Institutes of Health under grant numbers CA114889 and CA033572. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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