Philip O. Livingston, MD

2010-2011 BCRF Project:
Co-Investigator: Teresa A. Gilewski, MD, Memorial Sloan-Kettering Cancer Center, New York

Drs. Livingston and Gilewski and colleagues have prepared vaccines against a series of antigens that are expressed on the surface of most breast cancer cells and identified six antigens that were particularly effective in previous trials at inducing an immune response in vaccinated breast cancer patients. Last year, these researchers finished testing the final conjugate, readied the individual components for vaccine vialing, and settled on the trial design. In 2010-2011, they will combine these conjugates into a single hexavalent vaccine and to administer it to 10 patients in combination with second or third line chemotherapy. Through these trials, the Livingston-Gilewski team will be able to assess the safety and immunogenicity of this vaccine. They will also demonstrate this conjugate's impact on circulating tumor cells and time to progression.

Mid-year Progress: Drs. Livingston and Gilewski have identified six widely expressed breast cancer cell surface antigens and were able to induce consistent antibodies against each with properly constructed conjugate vaccines. They propose now to combine these conjugates into a single hexavalent vaccine and initiate a pilot study that will evaluate the vaccine alone in patients with metastatic breast cancer and evaluate second or third line chemotherapy with the vaccine. The goal of these studies is to determine the impact of high levels of cell surface reactive antibodies on circulating tumor cells (CTC). Over the last year, Drs. Livingston and Gilewski have gained experience in this patient population with the widely used but relatively insensitive Veridex CTC assay and selected a new, more sensitive CTC assay for use in the trials proposed here and for comparison to the Veridex assay. While reduction of CTC does not guarantee clinical benefit, in the absence of a reduction of CTC, clinical benefit is unlikely. The information obtained here concerning frequency of positive CTC with the flow cytometry assay in these second or third line chemotherapy patients will provide the basis for designing a larger clinical trial with progression free and overall survival as primary endpoints.

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.