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Vaccine Boosts Immunity Against Cancer Target


A therapeutic cancer vaccine being co-developed by the Ludwig Institute for Cancer Research (LICR) and the Australian biotechnology company CSL Limited successfully induced a comprehensive immune response in patients and appeared to delay cancer recurrence, according to a paper published today in the scientific journal, Proceedings of the National Academy of Sciences USA.

The study treated 46 patients, most with melanoma, with three monthly doses of the NY-ESO-1/ISCOMATRIXTM vaccine following surgical removal of the tumor. The vaccine combines a cancer-specific protein, the NY-ESO-1 antigen, with an immune stimulant, the ISCOMATRIXTM adjuvant, from CSL Ltd. In the study, some patients received different doses of the NY-ESO-1/ISCOMATRIXTM vaccine, some received the NY-ESO-1 protein without the ISCOMATRIXTM complex, and some received an inactive placebo. Detailed studies of the patients’ immune responses revealed that the NY-ESO-1/ISCOMATRIXTM vaccine, in contrast to vaccination with the placebo, induced the production of antibodies, and CD8 and CD4 T cells that target the NY-ESO-1 antigen. Vaccination with the NY-ESO-1 protein alone induced fewer responses than the NY-ESO-1/ISCOMATRIXTM vaccine.

“These results are very exciting,” says Dr. Jonathan Cebon, Head of the Joint Austin Health/Ludwig Institute Oncology Unit in Melbourne. “They show that it is possible to stimulate an integrated immune response that has the potential to attack cancer from a number of different angles. Being able to get antibodies, together with both types of T cells, gives us enormous confidence that we are heading in the right direction to develop a clinically effective therapy.”

According to Dr. Cebon, the vaccine also appeared to delay the recurrence of cancer, suggesting that some form of protection is being conferred by the vaccine. “Experience tells us that relapse within the next five years is quite likely in this patient group. So we had a unique opportunity to gather preliminary data on the vaccine’s effect by comparing, over a relatively long period of time, the progress of the group that received the vaccine with the progress of the group that did not.” In a review of the melanoma patients two years later, the researchers found that cancer recurred in five out of seven patients who received the placebo and nine out of 16 who received just the NY-ESO-1 protein. However, of the patients who received the full NY-ESO-1/ISCOMATRIXTM vaccine, 14 out of 19 remained cancer-free.

Despite the encouraging clinical results, the team is quick to point out that this type of retrospective analysis is considered less exact than had it been done in a planned, prospective fashion. “In interpreting these data, we need to be mindful that there may be unforeseen variables that we didn’t control for when we set up the trial,” warns Dr. Ian Davis from the LICR Melbourne Branch, the lead author of the clinical study. “And of course this is a small number of patients.”

The Cancer Vaccine Collaborative (CVC), a partnership established between the international LICR and the Cancer Research Institute (CRI) in New York, will now conduct a large, randomized study of NY-ESO-1/ISCOMATRIXTM vaccine in advanced metastatic melanoma to determine if the immunological and clinical responses do correlate, and whether the vaccine can indeed prevent cancer recurrence. The Phase II study will commence at clinical trials centers in Australia, New Zealand, and the United Kingdom in 2005.

The published studies were supported by the Ludwig Institute for Cancer Research (LICR). The clinical component of the study was conducted at the Austin Hospital, and the Peter MacCallum Cancer Center in Melbourne, Australia. The research team was comprised of researchers from the Melbourne Branch of the LICR based at Austin Hospital, the New York Branch of the LICR in the USA, and the Department of Pathology at Weill Medical College of Cornell University, New York NY, USA. Researchers from CSL Limited, Melbourne, Australia, also contributed to this investigation.

| newswise
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