Immunotherapeutic Strategies in Breast Cancer: Preclinical and Clinical Trials
Abstract
This project is focused on novel tumor vaccines directed at MUC1 and other tumor antigens. The authors' specific aims are as follows: (1) to assess the effectiveness of vaccines against MUC1 and other tumor antigens in the prevention and treatment of spontaneous breast carcinomas in mice, and (2) to translate an effective vaccine strategy into a phase I clinical trial in patients with undetectable disease following standard therapy. The model of spontaneous mammary cancer is the MUC1-expressing polyoma middle T antigen mice (MMT). The authors have tested five vaccines in the preclinical mouse model: (1) liposomal MUC1 tandem repeat peptide, (2) dendritic cells (DCs) pulsed with tumor lysate, (3) DCs fused to MMT tumor cells, (4) adoptive transfer of MUC1-specific cytotoxic T lymphocytes (CTLs) with CD137 co-stimulation, and (5) MUC1 peptides with CpG ODN and GM-CSF as adjuvants. Results show that all the vaccines elicited a strong immunological response. Adoptive transfer of MUC1-specific CTLs with co-stimulation (CD137 mAb) significantly reduced tumor burden and tolerance in MMT mice. The peptide vaccine prevented MUC1-expressing tumor growth. The clinical trial is in the final stages of review. It is a phase I trial testing MUC1 and HER-2/neu class I and class II peptides with CpG ODN and GM-CSF adjuvants in breast cancer patients free of disease.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2004
- Accession Number
- ADA435278
Entities
People
- Sandra J. Gendler
Organizations
- Mayo Clinic Scottsdale