Philip O. Livingston, MD

2009-2010 BCRF Project:
Co-Investigator: Teresa A. Gilewski, MD, Memorial Sloan-Kettering Cancer Center, New York

The investigators have prepared vaccines against a series of antigens that are expressed on the surface of most breast cancer cells and identified six (globo H, sLea, MUC1, Tn, TF and sTn) that were particularly effective in previous BCRF supported trials at inducing an immune response in vaccinated breast cancer patients. This includes the most recent addition (sLea) which has induced an antibody response in five consecutive patients in a currently ongoing BCRF supported trial. They plan to complete this small trial over the next two months.

During the next funding period they will prepare a vaccine containing all six of these breast cancer antigens, a hexavalent vaccine, and initiate a small pilot trial to determine the best way to combine this vaccine with systemic chemotherapy. Finally, they will initiate a randomized, double blind Phase II trial comparing chemotherapy plus non-specific immunization (immunological adjuvant OPT-821) to chemotherapy plus specific immunization against breast cancer (the hexavalent vaccine plus OPT-821). Approximately 120 patients with progressive breast cancer who are candidates for second or third line chemotherapy will be accrued, randomized and treated at MSKCC over a two year period.

Mid-Year Progress Report:
During the next six months, Drs. Livingston and Gilewski will prepare a vaccine containing all six of these breast cancer antigens, a hexavalent vaccine, and initiate a small pilot trial to determine the best way to combine this vaccine with systemic chemotherapy. Two groups of approximately 12 patients each with progressive breast cancer who are candidates for second or third line chemotherapy will be accrued to this pilot trial at MSKCC over the next 6-8 months. The researchers' goal is to follow this with a randomized, double blind Phase II trial comparing chemotherapy plus non-specific immunization (immunological adjuvant OPT-821) to chemotherapy plus specific immunization against breast cancer (the hexavalent vaccine plus OPT-821).

Bio:
Philip Livingston is Professor of Medicine and head of the Tumor Vaccinology laboratory at Memorial Sloan-Kettering Cancer Center. While recently the focus of this laboratory has included approaches for augmenting T-cell immunity against tumor antigens such as KSA and CA125, the focus for most of the last 25 years has been on tumor vaccines designed to induce antibodies against cancer cell surface antigens. These vaccines are now able to induce consistent antibody responses against a series of cell surface carbohydrate and protein antigens.

Recently, the individual monovalent vaccines have been combined into a polyvalent vaccine for breast cancer containing 7 different conjugates. A Phase II trial with this vaccine in patients with breast cancer is planned for the near future. This will determine whether vaccine induced antibodies against multiple cell surface antigens are able to prolong disease free and overall survival after surgical resection of all known disease and adjuvant chemotherapy.