Immunotherapeutic Strategies in Breast Cancer: Preclinical and Clinical Trials
Abstract
This project is focused on the development of novel tumor vaccines directed at MUC1 and other tumor antigens. Our specific aims are: 1) To assess the effectiveness of vaccine formulations against MUC1 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, although CTLs in the tumor environment were tolerized. DCs pulsed with lysate accompanied by co-stimulation (4-lBB) greatly reduced tumor burden and reduced tolerance in MMT mice. Aim 2, to develop a clinical trial, is underway. The clinical trial protocol is under review. It is a phase I trial testing MUCl and HER-2/neu class I and class II peptides in breast cancer patients free of disease.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2003
- Accession Number
- ADA421050
Entities
People
- Sandra J. Gendler
Organizations
- Mayo Clinic Scottsdale