Fusions of Breast Carcinoma and Dendritic Cells as a Vaccine for the Treatment of Metatastic Breast Cancer
Abstract
The overall objective of the project is to study the safety, immunologic response, and clinical effect of vaccination with dendritic cell (DC)/breast cancer fusions administered in conjunction with IL-12 in patients with metastatic breast cancer. Fusion of autologous tumor cells with DCs presents the entire repertoire of tumor antigens, including those yet to be identified, in the context of DC-mediated costimulation. The fusion cell vaccine allows for induction of helper T and CTL responses by class II presentation of exogenous protein and class I presentation of newly synthesized endogenous protein. Vaccination with fusion cells has eradicated established tumor in diverse animal models. In human MUC1 transgenic mice, vaccination with fusion cells reverses immunological unresponsiveness to MUC1 and results in the rejection of MUC1-positive tumors. Preclinical studies with patient-derived breast cancer cells and DCs have also demonstrated that fusion cells induce tumor-specific CTL responses and lysis of 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 31, 2010
- Accession Number
- ADA538750
Entities
People
- Baldev Vasir
- David Avagan
- Donald W. Kufe
Organizations
- Dana–Farber Cancer Institute