Correlation between tumor regression and T cell responses in melanoma patients vaccinated with a MAGE antigen.

Abstract

The cancer-germline gene MAGE-3 codes for tumor-specific antigens recognized on many tumors by T lymphocytes. A MAGE-3 antigen presented by HLA-A1 has been used in several vaccination trials on metastatic melanoma patients. Only a small minority of patients have shown evidence of tumor regression. Attempts to correlate the tumor rejections with the cytotoxic T lymphocyte (CTL) response against the vaccine have been hampered by the low level of these responses. In noncancerous individuals, the frequency of the T cell precursors against antigen MAGE-3.A1 is approximately 4 x 10(-7) CD8 T cells. The diversity of the T cell receptor repertoire of these anti-MAGE-3.A1 precursors was analyzed in one individual. The results indicate that it is very likely that the repertoire comprises >100 clonotypes. On this basis, it is possible to use not only the frequency of CTL precursors in the blood but also the presence of dominant clonotypes to ascertain in patients the existence of anti-MAGE-3.A1 responses as low as 10(-6) of CD8. With this approach, we observed a correlation between tumor regression and anti-MAGE-3.A1 CTL responses in patients vaccinated with a recombinant virus encoding the antigen and also in patients vaccinated with peptide-pulsed dendritic cells. In contrast, for patients showing tumor regression after vaccination with peptide alone, CTL responses were almost never observed. It is possible that even those CTL responses that are below our present detection level can trigger a sequence of events that leads to tumor regression.

• Authors: Christophe Lonchay, Pierre van der Bruggen, Thierry Connerotte, Takeshi Hanagiri, Pierre Coulie, Didier Colau, Sophie Lucas, Aline Van Pel, Kris Thielemans, Nicolas van Baren, Thierry Boon
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 101 Suppl 2 Pg. 14631-8 (Oct 05 2004) ISSN: 0027-8424 [Print] United States
• PMID: 15452345 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• Cancer Vaccines
• Complementarity Determining Regions
• MAGEA3 protein, human
• Neoplasm Proteins

Topics

• Amino Acid Sequence
• Antigens, Neoplasm (genetics)
• Canarypox virus (genetics)
• Cancer Vaccines (genetics, immunology, therapeutic use)
• Cell Line, Tumor
• Complementarity Determining Regions
• Cytotoxicity, Immunologic
• Dendritic Cells (immunology)
• Humans
• In Vitro Techniques
• Melanoma (immunology, secondary, therapy)
• Neoplasm Proteins (genetics)
• T-Lymphocytes, Cytotoxic (immunology)