Towards a clinical vaccine for prostate cancer A prostate cancer vaccine placed within an adenovirus – a common virus that typically causes cold-like symptoms – has been shown to be effective in model systems in the laboratory. Health © Image Point Fr, Shutterstock Prostate cancer is the second most common cancer in men in Europe. Almost 500 000 men in Europe are diagnosed with the cancer every year, and over 100 000 of them will die of it. The disease places a huge burden on patients, family members and the diagnostic and treatment healthcare services of every European country. “Efforts have been made to develop immunological approaches to prostate cancer with very limited success,” explains ONCOVIRVAX project coordinator Peter Selby, professor of Cancer Medicine at the University of Leeds, UK. “The problem is that prostate cancer does not stimulate a strong immune response in patients. To develop a vaccine, the cancer must be manipulated in such a way to stimulate a stronger immune response, in a controlled clinical setting.” Stimulating immune responses To address this challenge, the EU-funded ONCOVIRVAX project applied state-of-the-art immunological techniques to evaluate the immune response to prostate cancers in both mice and human cells. It also built on some groundbreaking work. “We were able to apply our previous collaborative experience in successfully developing a virus library of vaccines for the skin cancer melanoma,” explains Selby. “We demonstrated that it was possible to express a library of antigenic determinants for melanoma in a virus.” Antigenic determinants are the portion of foreign proteins that are capable of stimulating an immune response. The researchers found that, when placed in a virus and used to immunise mice, this technique produced a profoundly effective anti-cancer immune response. The challenge, as Selby points out, is to transfer these results to humans and produce a vaccine that can be used to treat patients. In the ONCOVIRVAX project, Selby and his team sought to express the antigenic determinants of the prostate cancer in the form of an immunogenic virus. “The hypothesis was that, by preparing a very large number of antigenic determinants and by placing them within the virus, we would get immune responses to a significant number of determinants,” explains Selby. “This would then produce an effective anti-cancer response.” Antigenic determinants from prostate cancer cells were prepared and then expressed in an adenovirus. “We chose an adenovirus because it was likely to be clinically safe,” says Selby. “We then used proteomic and genomic approaches to identify biomarkers associated with an immune response against cancer in the model systems.” Towards a vaccine During the course of the project, the team discovered several novel mechanisms by which cancers can provoke an immune response, something that could be critical to future vaccine development. “Although the strength of the immune response we generated was modest and the effect on prostate cancers in mice was also modest, progress has been made,” says Selby. Such approaches could prove particularly useful in the prevention of prostate cancer in high risk groups, and in the prevention of relapse and metastatic disease in patients who have had successful treatment of a localised cancer. Work carried out by ONCOVIRVAX could provide the basis for the production of a more immunogenic vaccine. “We’ll continue to work within the wider collaborative group, including with our key collaborator Richard Vile from the Mayo Clinic in the United States. Our aim is to increase the effectiveness of the vaccine both for prostate cancer and for other cancers,” says Selby. Keywords ONCOVIRVAX, vaccine, prostate, cancer, virus, adenovirus, melanoma, cells, immune
