By Vicki Brower

Special To BioWorld Today

The University of California at San Francisco (UCSF) received approval and support from the National Cancer Institute (NCI) to combine liposomes with chemotherapy and antibodies to target and kill cancer cells.

The collaboration will produce what UCSF researchers call "immunoliposomes," which are selectively targeted — like Gulf War "smart bombs" — to seek out and kill cancerous cells while avoiding normal cells.

Due to their specificity, immunoliposomes are expected to be less toxic than other cancer therapies, said one of the drug's developers, John Park, assistant adjunct professor of medicine. Other UCSF researchers include Christopher Benz, Demetrios Papahadjopoulos, Dmitri Kirpotin and Keelung Hong.

Liposomes have been approved in the U.S. for use in chemotherapeutics for Kaposi's sarcoma patients, and are now being tested in breast cancer. The UCSF immunoliposomes will carry the chemotherapeutic doxorubicin to cancer cells, guided by an anti-HER2/neu antibody, which "recognizes" the HER2 receptor on the surface of breast cancer cells. Unlike antibody therapies, "we're not just targeting the protein, but using the liposome component to bring a payload of chemotherapy to the cancer cells," said Park.

The HER2/neu antigen is overexpressed in breast and numerous other cancers. The combination of antibody and liposome technologies is designed to have a greater effect on breast cancer cells than either technology alone.

The antibody used was developed in the laboratory of James Marks, UCSF associate professor of anesthesia and pharmaceutical chemistry. Genentech Inc., of South San Francisco, also is developing an anti-HER2/neu antibody for use alone and with chemotherapy; its antibody combined with doxorubicin is now completing Phase III trials in breast cancer.

UCSF's immunoliposomes deliver doxorubicin to cancer cells in a manner that is different from plain liposomes, because the antibody allows the immunoliposomes to directly target cancer cells.

Liposomes without targeting can accumulate within tumor tissue, but do not interact with tumor cells, and instead rely on eventual liposome breakdown and drug diffusion.

"Our immunoliposomes selectively bind to tumor cells and then internalize, resulting in intracellular drug delivery," Park told BioWorld Today. Clinical trials for breast cancer are expected to begin within a year.

An added benefit to the combination: the drug is less toxic to such sites as the heart and bone marrow when given in immunoliposomes rather than as free drug.

The idea of developing immunoliposomes is not new. Scientists have considered doing just that for more than a decade, Park said, but there have been numerous practical problems involving the right combination of liposomes, antibodies and targets.

UCSF's research with liposomes is being sponsored by the NCI's Breast Cancer Specialized Programs of Research Excellence — the SPORE program. The UCSF program is one of 15 nationwide that is receiving special funds from the NCI to accelerate research to the clinic.

Funding also is provided by the U.S. Department of Defense and the American Society of Clinical Oncology. *