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Vaccine that combines a synthetic bacterial DNA sequence and melanoma antigen shows promise in phase I trial

A cancer vaccine that combines a commercially produced bacterial DNA sequence with a peptide antigen found on melanoma cells has shown promise in a phase I trial, according to an article in the February issue of the Journal of Clinical Investigation.

The Swiss-American team found that the CpG 7909 DNA sequence (ProMune-, Coley Pharmaceutical) 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 in the framework of the international Cancer Vaccine Collaborative, a partnership established by the New York-based Cancer Research Institute and the Ludwig Institute.

“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,” said lead author Dr. Daniel Speiser. “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 with a synthetic peptide 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 Cancer Research Institute, the trial is part of a 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, 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.”

Clinical research sites are located in Australia, Belgium, Germany, Japan, Switzerland, the United Kingdom, and the USA.


 


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