Fusions of Breast Carcinoma and Dendritic Cells as a Vaccine for the Treatment of Metastatic Breast Cancer. Addendum
Final addendum rept. 1 Jul 2008-30 Jun 2009
DANA-FARBER CANCER INST BOSTON MA
Pagination or Media Count:
The overall objective of the project is to study the safety, immunologic response, and clinical effect of vaccination with dendritic cell DCbreast cancer fusions administered in conjunction with IL-12 in patients with metastatic breast cancer. DCbreast carcinoma fusion cells present a broad array of tumor associated antigens in the context of DC-mediated co stimulation. Fusion cells stimulate tumor specific immunity with the capacity to lyse autologous tumor cells. In clinical studies, vaccination with fusion cells was well tolerated, induced immunologic responses in a majority of patients, and results in disease regression in subset of patients. We postulated that administration of the vaccine in conjunction with IL-12 would further enhance vaccine response by promoting T cell activation. In the first 3 years of the grant, we examined DCbreast carcinoma fusions with respect to their phenotypic characteristics as antigen presenting cells and their capacity to stimulate anti-tumor immunity. We demonstrated that DCbreast carcinoma fusions strongly express co stimulatory, adhesion, and maturation markers as well as the stimulatory cytokines, IL-12 and IFNgamma. In addition, fusion cells expressed CCR7 necessary for the migration of cells to sites of T cell traffic in the draining lymph nodes. In concert with these findings, fusions generated with immature and mature DCs potently stimulated CTL mediated lysis of autologous tumor targets.
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