Pathogen-mimicking vaccine as strategy for cancer therapy

(Lausanne, February 3rd) - Results from the first clinical trial of a therapeutic cancer vaccine combining the synthetic bacterial DNA sequence, CpG 7909 (ProMune^TM, Coley Pharmaceutical), with a peptide antigen were reported today in the Journal of Clinical Investigation. The paper shows that the CpG 7909 DNA sequence is safe, and increases the immune system's ability to recognize and destroy cancer cells. The Phase I study was conducted by the Lausanne Branch of the Ludwig Institute for Cancer Research (LICR) at the Lausanne University Hospital in Switzerland, in the framework of the international Cancer Vaccine Collaborative (CVC), a partnership established by the New York-based Cancer Research Institute (CRI) and the LICR.

"What we're doing is testing a novel adjuvant, a compound that stimulates the immunological response to a vaccine, which is essentially tricking the immune system into thinking the vaccine is a bacterial infection," says lead author Dr. Daniel Speiser from the LICR Lausanne Branch. "The immune system mounts a response against the peptide antigen, the cancer-specific target, in the vaccine, and thus also against the antigen on the cancer cells."

The vaccine, combining the CpG 7909 adjuvant and Incomplete Freund's Adjuvant (IFA) with a synthetic peptide (protein fragment) from a melanoma antigen known as Melan-A/MART-1, induced CD8+ T cells that specifically recognized cells displaying Melan-A/MART-1 on their surface. This T cell response occurred in all eight patients in the trial. Responses were one order of magnitude higher than those observed in eight patients who received the Melan-A/MART-1 antigen with IFA but without CpG 7909 in previous studies.

According to Dr. Jill O'Donnell-Tormey, the Executive Director of CRI, the trial is part of the CVC's systematic, coordinated vaccine development approach that compares single vaccine variables in parallel. "We've identified many cancer antigens, and the challenge is to determine which cancer vaccine compositions induce a strong and sustained immune response against particular antigens. The results from this trial represent a substantial step forward in this regard. This conclusion is justified because we are using reproducible immunological monitoring across the CVC, allowing a more accurate comparison of the effects of CpG 7909 in this trial with the results of several other adjuvants that have been tested in other trials. By comparing single variables in parallel we believe we can develop effective cancer vaccines in a much shorter time than the conventional approach of trying variables sequentially." The CVC has clinical research sites in Australia, Belgium, Germany, Japan, Switzerland, the UK and the USA.

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