Immunotherapeutic Strategies in Breast Cancer: Preclinical and Clinical Trials
Abstract
This project is focused on the development of novel tumor vaccines directed at MUCl and other tumor antigens. Our specific aims are: 1) To assess the effectiveness of vaccine formulations against MUCl and other tumor antigens in the prevention and treatment of spontaneous breast carcinomas in mice and 2) To translate the most effective vaccine strategies into phase I clinical trials in patients with high and low tumor burden. The model of spontaneous mammary cancer is the MUCl-expressing polyoma middle T antigen mice (MMT). We have tested four vaccines in the preclinical mouse model: 1) liposomal MUCl tandem repeat peptide, 2) dendritic cells (DCs) pulsed with tumor lysate, 3) DCs fused to MMT tumor cells, and 4) adoptive transfer of MUCl-specific cytotoxic T lymphocytes (CTLs). All vaccines elicited a strong immunological response, delay of tumor growth and development of mature MUCl-specific CTLs. Failure to eradicate the large tumor burden in these mice appears to be due to the development of tolerance in the CTLs within the tumor environment. Tumors also exhibited several known escape mechanisms. Future studies will test strategies that should prevent or over-ride the development of tolerance. The clinical trial protocol is under development.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2002
- Accession Number
- ADA410811
Entities
People
- Sandra J. Gendler
Organizations
- Mayo Clinic Scottsdale