BioWorld International Correspondent
PARIS - A technology that uses exosomes derived from immune system cells as vectors for anticancer vaccines is being tested in clinical trials in France and the United States by a Franco-American company called Anosys Inc.
Following successful Phase I/II trials in France and the U.S., the company is scheduled to embark on a multicenter Phase II trial in the same countries in 2003, having already obtained approval from their respective regulatory authorities.
Although based in Menlo Park, Calif., Anosys was founded by two French researchers who were previously with Strasbourg, France-based Aventis, which is one of Anosys' three major shareholders, the other two being the Japanese company Kirin and the venture capital firm Bank Invest, of Copenhagen, Denmark. The company was created at the end of 1997 and has raised total funds of US$35 million since then.
It established a French subsidiary Anosys SA, which now has established a research and development center at Evry, the site of France's national biotechnology science and business park. The company's vice president of European operations, Vincent Serra, told BioWorld International that the center includes GMP manufacturing facilities with the capacity to produce all the clinical batches required for the planned trials.
Anosys is applying technology developed by researchers at the Institut Curie in Paris and the French National Institute of Health and Medical Research (INSERM), who are publishing the results of their work in a paper titled "Indirect activation of naive CD4+T cells by dendritic cell-derived exosomes" in the December 2002 edition of Nature Immunology.
Anosys acquired exclusive licenses to this technology in 1998, as well as to other patents covering exosomes held by the Dutch universities in Leiden and Utrecht. Altogether, it owns rights to more than 50 patents in the areas of exosome production/purification and use, dendritic cell isolation, processing and use, synthetic exosomes, recombinant exosomes, and the delivery and use of tumor-associated antigens.
Exosomes are spherical vesicles, 30 nanometers to 100 nanometers in diameter, formed by cells to facilitate intercellular communication. It is believed that several different types of cells secrete exosomes, especially immune system cells like mastocytes, T- and B-lymphocytes, dendritic cells and platelets.
Anosys is focusing on exosomes derived from dendritic cells, known as dexosomes, that activate various immune system cells. The activation of these various immune cells amplifies the original signal provided by disease antigens and thus generates a stronger immune response.
To set in motion a tumor rejection reaction in the organism, dexosomes are loaded with a specific tumor antigen, and in vitro and in vivo studies in mice demonstrated that dendritic cells previously exposed to tumor antigens induced tumor rejection. It was then decided to explore the use of exosomes as vaccine vectors for preventing tumor relapse caused by cancerous cells having escaped initial treatment - a hypothesis confirmed in further mouse studies.
The larger-scale Phase II trial, which will be in the same two indications, is due to get under way at several hospitals in the U.S. in the first quarter of 2003 and later at the two French cancer centers. Serra added that further Phase I/II trials are planned in other indications, including one in cervical cancer in France in 2003.