Fusions of Breast Carcinoma and Dendritic Cells as a Vaccine for the Treatment of Metatastic Breast Cancer.
Abstract
The purpose of the study was to determine the effectiveness, safety, immunologic response, and clinical activity of vaccination with dendritic cell (DC)/breast cancer fusions administered in conjunction with IL-12 in patients with metastatic breast cancer. DC/breast carcinoma fusion cells present a broad array of tumor-associated antigens in the context of DC-mediated costimulation. Our pre-clinical studies showed that fusion of DCs with breast carcinoma cells up-regulates expression of costimulatory and maturation markers, results in high levels of expression of IL-12, and stimulates a mixed T cell response characterized by the expansion of both activated and regulatory T cell populations. Our results further showed that IL-12, IL-18, and TLR 9 agonist CpG oligodeoxynucleotides reduced the level of fusion- mediated regulatory T cell expansion and that sequential stimulation of fusion cells with anti-CD3/CD28 resulted in marker expansion of activated tumor-specific T cells. These findings indicated that DC/breast carcinoma fusions are effective in combination with IL-12 in activating antigen-specific T cells in clinical studies, vaccination of patients with metastatic breast cancer with fusion cells was well tolerated and induced immunologic responses. Combination of the vaccine with IL-12 was delayed by a lengthy review process, issues relating to the availability of IL-12 from the NCI and the challenge of enrolling patients with accessible tumor tissue for generating the vaccine. As a result, the present trial was closed and the plan is to develop this approach for breast cancer patients as adjuvant therapy following primary surgery.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2013
- Accession Number
- ADA599377
Entities
People
- Baldev Vasir
- David Avigan
- Donald Kufe
Organizations
- Dana–Farber Cancer Institute