Breast Cancer Vaccines Based on Dendritic Cells and the Chemokines
Abstract
The major objective of this project is to establish a new modality for the treatment of breast cancer that employs the combination of chemokine gene modified fibroblasts with breast tumor pulsed dendritic cells (DC) to both recruit and/or concentrate from the periphery low frequency immune reactive T cells as well as to potently stimulate these effector cells once localized at the vaccination site. During the first year of this four-year project, studies focused on two major areas specified in the Statement of Work: (1) to optimize human DC generation and function; and (2) to construct expression vectors containing chemokine cDNAs for subsequent gene transfer into fibroblasts. Marked enhancement of human peripheral blood-derived DC number and function (i.e. presentation of tetanus and candida antigens as well as stimulation of primary allogeneic mixed leukocyte response) could be achieved by the addition of TNF alpha to cultures containing the combination of GM-CSF and 1L-4. DC obtained from advanced breast cancer patients could potently stimulate the generation of autologous, KLH-specific CD4+ T cells in vitro. Construction of retroviral vectors based on the MFG backbone and production of retroviral supematants at high titer by a transient packaging cell system have been accomplished, which have resulted in successful chemokine (i.e. RANTES, Lymphotactin, MIP-1 Beta) gene transfer into fibroblasts. Collectively, the data provided in this annual report demonstrate successful completion of studies according to the proposed year 1 timeline in the grant application.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1997
- Accession Number
- ADA332859
Entities
People
- James J. Mule
Organizations
- University of Michigan