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the patrick c. walsh prostate cancer research fund

Creating a Vaccine Against Prostate Cancer

Trying to work around prostate cancer's impressive ability to defend itself is like a molecular game of chess. The technology is there; now the key is to figure out the best strategy.

Can a man be inoculated against his own prostate cancer? Scientist Raphael Viscidi, M.D., along with co-investigators Brian Simons and Ashley Ross, hopes to find out. "Because the disease can be diagnosed early and the prostate expresses tissue-specific proteins that can be the target of vaccines, we are investigating the value of a novel vaccine for prostate cancer in an animal model," says Viscidi. To make the vaccine, they are using a virus — actually, part of a virus, a protein that has the ability to form a large particle. "The outer surface of the particle can be decorated with short proteins," — think of sprinkles on a cupcake — "and these will be derived from tissue-specific proteins made by prostate cancers. We have shown that these novel particles can induce immune cells," enlisting the body in the fight against prostate cancer.

"The physical properties of the particles make them very potent inducers of cellular immune responses," Viscidi explains. "Unlike most other vaccines, they can be administered on their own to induce immune responses. We are using three tissue-specific proteins made by prostate cancers: prostatic acid phosphatase, prostate stem cell antigen, and stimulator of prostate adenocarcinoma-specific T cells." In work supported by the Patrick C. Walsh Prostate Cancer Research Fund, the investigators will dot the surface of the vaccine particles with small proteins known to specifically stimulate the immune system of mice.

What the team is doing, trying to work around prostate cancer's impressive ability to defend itself, is like a molecular game of chess. The technology is there; now the key is to figure out the best strategy. For example, Viscidi says, "cancers have recently been shown to block immune responses by expressing inhibitory proteins." Two of these proteins are CTLA4 and TIM-3. But in a counter move, scientists have developed antibodies that block these proteins. Will it strengthen the immune response if the investigators combine their vaccine with these anti-CTLA4 and anti-TIM-3 antibodies? They plan to find out, using a model known as the TRAMP mouse. "The advantage is that these spontaneously develop cancer in the prostate gland. We will treat mice of various ages, representing stages of prostate cancer from small lesions to metastatic disease, with our vaccine alone or in combination with anti-CTLA4 and anti-TIM-3 antibodies. If the vaccine proves successful in treating cancers in the mouse model, we plan to construct a similar vaccine using human prostate-specific proteins, and test it in men with prostate cancer."

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