Identification of antigens recognized by T lymphocytes on human tumors, and pilot vaccination studies with defined antigens

• Forschungsstelle: EU FRP
• Projektnummer: 95.0413
• Projekttitel Englisch: Identification of antigens recognized by T lymphocytes on human tumors, and pilot vaccination studies with defined antigens

Schlüsselwörter (Englisch)

Tumor antigens - CD8+ T cells; cancer vaccines; melanoma

Alternative Projektnummern (Englisch)

EU project number: BMH4CT951627

Forschungsprogramme (Englisch)

EU-programme: 4. Frame Research Programme - 4.2 Agriculture and agroindustry

Kurzbeschreibung (Englisch)

See abstract

Partner und Internationale Organisationen (Englisch)

Université catholique de Louvain, Istituto Nazionale per lo Studio e Ia Cura dei Tumori, Rijksuniversiteit Leiden, Deutsches Krebsforschungzentrum

Abstract (Englisch)

The main focus of our work has included a detailed study of the immunogenicity in vitro and in vivo of the CTL-defined melanoma antigen called Melan-A/MART-1. This antigen is expressed by normal melanocytes as well as by most fresh melanoma samples. Melan-A specific CTL have been identified in both peripheral blood mononuclear cells and tumor-infiltrating lymphocytes from HLA-A*O2O1 melanoma patients. While initial studies identified peptide Melan-A 27-35 as the immunodominant epitope, we found that peptide Melan-A 26-35 was better recognized by the majority of Melan-A specific CTL clones tested. Moreover, we identified Melan-A peptide analogues which not only bound more avidly to HLA-A*O2O1 molecules but, more importantly, were recognized better than the natural antigenic peptides by Melan-A specific CTL clones. Furthermore, in vitro generation of Melan-A specific CTL by stimulation of peripheral blood mononuclear cells from HLA-A*O2O1 melanoma patients with a selected peptide analogue was much more efficient than that observed with either one of the two natural peptides. A second aspect of our activity has been devoted to the assessment of novel methods to monitor antigen-specific CTL responses in an animal tumor model and in melanoma patients immunized with peptide-based vaccines. In particular, we have applied the recently developed technique based on the use of tetrameric forms of soluble peptide-MHC ligands for TCR to the enumeration of antigen-specific CD8+ T cells in lymphoid organs and peripheral blood. Altogether, our studies indicate that a) future peptide-based vaccine trials in melanoma should include Melan-A peptide analogues, and b) CTL responses elicited by such vaccines should be quantitatively assessed by the 'tetramer' technique.

Datenbankreferenzen (Englisch)

Swiss Database: Euro-DB of the
State Secretariat for Education and Research
Hallwylstrasse 4
CH-3003 Berne, Switzerland
Tel. [phone]
Swiss Project-Number: 95.0413