By Peter Winter

Special To BioWorld Today

TORONTO -- Pasteur Merieux Connaught (PMC) France has signified its intention to become a major player in the race to develop and market effective cancer vaccines. And Canadian biotechnology is likely to benefit from the initiative.

With Prime Minister Jean Chretien and federal Industry Minister John Manley in attendance, Jean Jacques Bertrand, chairman and CEO of Pasteur Merieux Connaught, of Paris, said Wednesday the company will invest up to C$350 million over 10 years in a new cancer vaccine research initiative.

The project represents the largest biotechnology investment ever made in Canada, Chretien said. He also took the opportunity to convey a "signal to the rest of the world" of the commitment the government has in supporting the considerable scientific and technological research expertise that Canada possesses.

In addition to the quality of Canadian research, another major factor in the French parent's decision to award the company's Canadian subsidiary, Pasteur Merieux Connaught Canada, a mandate for the development, manufacture and export of any products derived from the initiative was the federal government's financial contribution of up to C$60 million toward the initiative, made through its Technology Partnerships Canada (TPC) program.

Maureen Lofthouse, director of Enabling Technology at TPC, in Ottawa, told BioWorld Today that the government's investment, representing about 22 percent of the program's eligible costs, will eventually have to be repaid. The repayment will be based on royalties tied to product sales, which have been projected to be as much as C$10 billion during the first 10 years of commercialization of any successful vaccines.

TPC is highly focused on firms involved in the areas of environmental technologies, enabling technologies such as biotech, and aerospace and defense, that meet rigid criteria. In particular, the companies should be financially sound, generate lasting, quality jobs during the partnership, and have clearly identified market opportunities. It is a vehicle designed to create partnerships and leverage private-sector spending on near-market development of products and processes.

Michel Kline, vice president of biotechnology research at PMC, in North York, Ontario, said with this project, "We are, in effect, creating a pan-Canadian center of excellence in reverse of the traditional model that Canada pioneered, and has been closely studied by other nations." Canada's Networks of Centres of Excellence program is principally designed to bring together research, mainly within university settings, to develop leading-edge technologies are then made available to industry receptors.

In the case of the cancer vaccine project, a receptor for the technology already is in place. By involving cancer researchers from across Canada in the project, PMC will be a receptor for intellectual property and a focal point for collaboration with universities, government agencies and industry.

The initiative is expected to eventually involve an estimated 60 organizations across Canada. Discussions are currently under way with a number of organizations, including the University of Toronto, The Clinical Research Centre (Montreal), The National Cancer Institute (Toronto), The B.C. Cancer Agency (Vancouver), Biomira Inc. (Edmonton) and The Alberta Research Council (Edmonton). As a result, the project could benefit from additional contributions of up to C$25 million. Further details on how the C$350 million will be dispersed were not revealed.

Klein said the focus of the research initiative will be tumor-specific immunotherapy and the enhancement of pre-existing cellular immunity in cancer patients. This can be achieved by educating, recruiting and amplifying clones of cytotoxic T-lymphocytes (CTL) that are specialized in the recognition and destruction of tumor cells. Tumor cells express tumor-associated antigens (TAA) on their surface. PMC's fundamental approach is to use proprietary poxvirus technology to engineer viral vectors producing TAAs and use these to immunize cancer patients.

A number of TAAs already have been identified, including CEA for colorectal cancers, Muc-1 for breast and pancreatic cancers and PSA for prostate cancer. The protocol that will be under examination in the cancer vaccine project is known as a prime boost immunization, Klein said. This involves an immunization schedule that will include a priming of patients with vectored TAAs, followed by a boost using either appropriately adjuvanted recombinant TAA subunits or lipidated synthetic CTL epitopes.

There have been significant developments in adjuvant technology in recent years. New generation adjuvants are under active research and development in order to generate greater vaccine-induced immunity. Currently, aluminum salts are the only adjuvant used in commercial vaccines. The research initiative will be investigating adjuvants as well as TAAs, peptide and carbohydrate technologies, immunomodulators and immunotargeting.

Initially, the research will focus on the development of therapeutic vaccines to treat melanoma, colorectal and cancers of the urogenital tract, such as bladder, prostate and cervical. The research will then be expanded to include breast, ovarian and lung cancer. In total, these cancers account for 66 percent of all cancer cases in Canada.

"We will be working collaboratively with leading Canadian researchers and organizations to provide proof of concept on the protocol and then validate the vaccines in the clinic," Klein said. Although most of the work will take place in Canada, Klein indicated there wouldn't be enough patients for later-stage clinical trials in Canada for some of the cancer indications. In those situations, clinical trials will be conducted internationally.

PMC Canada already manufactures a therapeutic cancer treatment. ImmuCyst, the company's BCG immunotherapeutic which was developed at its Toronto facility, has proven to be 83 percent effective in the treatment of superficial bladder cancer and is licensed and sold in more than 40 countries. *