Melan-A/MART1 analog peptide triggers anti-myeloma T-cells through crossreactivity with HM1.24.
The Melan-A(aa26-35) (EAAGIGILTV) peptide is a human leukocyte antigen (HLA)-A2-restricted T-cell epitope within the Melan-A/MART-1 tumor antigen expressed on malignant melanoma cells. Melan-A and Melan-A analog (ELAGIGILTV, Melan-A(aa26-35*A27L)) specific T-cells can be expanded reliably for immunotherapeutic approaches in vitro. We studied the ability of Melan-A analog (ELAGIGILTV, Melan-A(aa26-35*A27L)) specific T-cells to recognize the HM1.24(aa22-30) (LLLGIGILV) peptide within the HM1.24 antigen presented by normal and malignant plasma cells. Peripheral blood mononuclear cells from HLA-A2+ healthy donors and HLA-A2+ multiple myeloma (MM) patients were stimulated with Melan-A analog peptide-loaded autologous dendritic cells, and expanded in vitro. T-cell activation was assessed by interferon-gamma specific enzyme-linked immunosorbent spot and cytotoxicity by (51)Chromium-release-assays. The frequency of Melan-A analog specific CD8+ T-cells was detected by using tetramers. Melan-A analog specific T-cells from HLA-A2+ healthy donors and HLA-A2+ MM patients showed a interferon-gamma secretion mediated by HM1.24(aa22-30) peptide-pulsed T2 cells and lysed the HLA-A2+ HM1.24+ U266 and XG-1 human myeloma derived cell-lines as well as the B-lymphoblastoid cell-line IM-9. Melan-A analog specific T-cells from MM patients specifically lysed autologous MM cells. The current data demonstrate that Melan-A analog specific T-cells crossreact with HM1.24(aa22-30). They might be a tool for the future use in immunotherapy against MM.
Christensen
Olaf
O
Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany. olaf.christensen@bayer.com
Lupu
Alaviana
A
Schmidt
Stefanie
S
Condomines
Maud
M
Belle
Sebastian
S
Maier
Ariane
A
Hose
Dirk
D
Neuber
Brigitte
B
Moos
Marion
M
Kleist
Christian
C
Terness
Peter
P
Ho
Anthony D
AD
Goldschmidt
Hartmut
H
Klein
Bernard
B
Hundemer
Michael
M
D015703:Antigens, CD / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D019496:Cancer Vaccines / Q000276:immunology; D045744:Cell Line, Tumor; D003429:Cross Reactions / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D058851:GPI-Linked Proteins; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D058965:MART-1 Antigen; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology*; D009101:Multiple Myeloma / Q000276:immunology* / Q000628:therapy; D009363:Neoplasm Proteins / Q000276:immunology*; D010455:Peptides / Q000276:immunology; D000074010:Bone Marrow Stromal Antigen 2
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D058851:GPI-Linked Proteins; D015789:HLA-A2 Antigen; D007371:Interferon-gamma; D058965:MART-1 Antigen; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D010455:Peptides; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2; C548667:MLANA protein, human