Vaccination of a melanoma patient with mature dendritic cells pulsed with MAGE-3 peptides triggers the activity of nonvaccine anti-tumor cells.

Abstract

We previously characterized the CTL response of a melanoma patient who experienced tumor regression following vaccination with an ALVAC virus coding for a MAGE-A3 Ag. Whereas anti-vaccine CTL were rare in the blood and inside metastases of this patient, anti-tumor CTL recognizing other tumor Ags, mainly MAGE-C2, were 100 times more frequent in the blood and considerably enriched in metastases following vaccination. In this study we report the analysis of the CTL response of a second melanoma patient who showed a mixed tumor response after vaccination with dendritic cells pulsed with two MAGE-A3 antigenic peptides presented, respectively, by HLA-A1 and HLA-DP4. Anti-MAGE-3.A1 CD8 and anti-MAGE-3.DP4 CD4 T cells became detectable in the blood after vaccination at a frequency of approximately 10(-5) among the CD8 or CD4 T cells, respectively, and they were slightly enriched in slowly progressing metastases. Additional anti-tumor CTL were present in the blood at a frequency of 2x10(-4) among the CD8 T cells and, among these, an anti-MAGE-C2 CTL clone was detected only following vaccination and was enriched by >1,000-fold in metastases relative to the blood. The striking similarity of these results with our previous observations further supports the hypothesis that the induction of a few anti-vaccine T cells may prime or restimulate additional anti-tumor T cell clones that are mainly responsible for the tumor regression.

• Authors: Javier Carrasco, Aline Van Pel, Bart Neyns, Bernard Lethé, Francis Brasseur, Nicolina Renkvist, Pierre van der Bruggen, Nicolas van Baren, Robert Paulus, Kris Thielemans, Thierry Boon, Danièle Godelaine
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 180 Issue 5 Pg. 3585-93 (Mar 01 2008) ISSN: 0022-1767 [Print] United States
• PMID: 18292586 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• MAGEA3 protein, human
• Neoplasm Proteins
• Peptide Fragments

Topics

• Amino Acid Sequence
• Antigens, Neoplasm (immunology, metabolism, therapeutic use)
• Cell Differentiation (immunology)
• Cell Line, Transformed
• Cytotoxicity Tests, Immunologic
• Dendritic Cells (immunology, metabolism, transplantation)
• Humans
• Immunotherapy, Adoptive (methods)
• K562 Cells
• Lymphocyte Count
• Lymphocytes, Tumor-Infiltrating (immunology, pathology)
• Melanoma (immunology, pathology, secondary, therapy)
• Molecular Sequence Data
• Neoplasm Proteins (immunology, metabolism, therapeutic use)
• Neoplasm Recurrence, Local (immunology, pathology, secondary, therapy)
• Peptide Fragments (immunology, metabolism, therapeutic use)
• Skin Neoplasms (immunology, pathology, secondary, therapy)
• T-Lymphocytes, Cytotoxic (immunology, metabolism, pathology)
• Tumor Cells, Cultured