Cellular immune responses against the cancer-testis antigen SPAN-XB in healthy donors and patients with multiple myeloma.
The cancer-testis antigen SPAN-XB has been recently identified in multiple myeloma (MM). In the present study, we identified and characterized for the first time a cytotoxic cellular immune response against SPAN-XB in healthy donors and patients with MM. Using two independent computer algorithms, two SPAN-XB-derived peptides (peptides 624 and 626) with predicted binding to HLA-A2 were identified. To further improve the immunogenicity of peptide 626 we designed a heteroclitic peptide (peptide 627) by modifying one amino acid on the HLA binding position 2 of peptide 626. Using an IFN-gamma Elispot assay we could demonstrate the presence and functional activity of CD8 peptide specific T cells with all tested peptides. By analysis of peripheral blood of 13 healthy donors and five patients with MM peptide specific T-cell precursors specifically recognizing at least one of the tested peptides could be detected and expanded in 9 of 13 of tested donors and 3 of 5 tested patients. Importantly, in two donors specific peptides could be generated against the heteroclitic peptide 627 but not against the native peptide 626. We conclude that SPAN-XB-derived peptides can elicit a consistent CD8 T cell response in healthy donors and patients with MM.
Frank
Christian
C
Department of Haematology and Oncology, University Hospital Heidelberg, Heidelberg, Germany.
Hundemer
Michael
M
Ho
Anthony D
AD
Goldschmidt
Hartmut
H
Witzens-Harig
Mathias
M
D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000628:therapy*; D009687:Nuclear Proteins / Q000276:immunology*; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology
D000951:Antigens, Neoplasm; D015789:HLA-A2 Antigen; D009687:Nuclear Proteins; D010455:Peptides; C518957:SPANXB1 protein, human