Pathogen-Mimicking Vaccine as Strategy for Cancer Therapy

Newswise — Results from the first clinical trial of a therapeutic cancer vaccine combining the synthetic bacterial DNA sequence, CpG 7909 (ProMuneâ„¢, 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.

This study was performed by investigators from the Ludwig Institute for Cancer Research Lausanne Branch, the Multidisciplinary Cancer Center at the Centre Hospitalier Universitaire Vaudois (CHUV), University of Lausanne, the Swiss Institute for Experimental Cancer Research, Lausanne-Epalinges, Switzerland, and the Coley Pharmaceutical Group, Wellesley MA, U.S.A.

The Cancer Vaccine Collaborative (CVC) is a partnership between two not-for-profit academic institutions that has developed an unparalleled program that conducts a systematic analysis in humans comparing immunological approaches to the creation of therapeutic cancer vaccines through a coordinated global effort.

The Ludwig Institute for Cancer Research (LICR) is the largest international academic institute dedicated to understanding and controlling cancer. With ten Branches in seven countries, and numerous Affiliates and Clinical Trial Centers in many others, the scientific network that is LICR quite literally covers the globe. The uniqueness of LICR lies not only in its size and scale, but also in its philosophy and ability to drive its results from the laboratory into the clinic. LICR has developed an impressive portfolio of reagents, knowledge, expertise, and intellectual property, and has also assembled the personnel, facilities, and practices necessary to patent, clinically evaluate, license, and thus translate, the most promising aspects of its own laboratory research into cancer therapies.

The Cancer Research InstituteSince its inception in 1953, the Cancer Research Institute (CRI) has had a singular mission—to foster research that will yield an understanding of the immune system and its response to cancer, with the ultimate goal of developing immunological methods for the control and prevention of the disease. To accomplish these goals, CRI supports scientists at all stages of their careers and funds every step of the research process, from basic laboratory studies to clinical trials testing novel immunotherapies. Guided by a Scientific Advisory Council, which includes 4 Nobel Prize winners and 24 members of the National Academy of Sciences, CRI awards fellowships and grants to scientists around the world. Additionally, the Institute has more recently taken on a new leadership role in the areas of preclinical and clinical research by serving as the integrating force and facilitator of collaborations among leading experts. CRI has thus become a catalyst for accelerating the development of cancer vaccines and antibody therapies.