In vitro and in vivo induction of a Th cell response toward peptides of the melanoma-associated glycoprotein 100 protein selected by the TEPITOPE program.
The melanoma-associated Ag glycoprotein 100 was analyzed by the T cell epitope prediction software TEPITOPE. Seven HLA-DR promiscuous peptides predicted with a stringent threshold were used to load dendritic cells (DC), and induction of a proliferative response was monitored. PBMC of all nine donors including two patients with malignant melanoma responded to at least one of the peptides. The proliferative response was defined as a Th response by the selective expansion of CD4(+) cells, up-regulation of CD25 and CD40L, and IL-2 and IFN-gamma expression. Peptide-loaded DC also initiated a T helper response in vivo (i.e., tumor growth in the SCID mouse was significantly retarded by the transfer of PBMC together with peptide-loaded DC). Because the use of the TEPITOPE program allows for a prediction of T cell epitopes; because the predicted peptides can be rapidly confirmed by inducing a Th response in the individual patient; and because application of peptide-loaded DC suffices for the in vivo activation of helper cells, vaccination with MHC class II-binding peptides of tumor-associated Ags becomes a feasible and likely powerful tool in the immunotherapy of cancer.
Cochlovius
B
B
Department of Tumor Progression and Immune Defense, German Cancer Research Center, Heidelberg, Germany.
Stassar
M
M
Christ
O
O
Raddrizzani
L
L
Hammer
J
J
Mytilineos
I
I
Zöller
M
M
D019264:Adoptive Transfer; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006131:Growth Inhibitors / Q000008:administration & dosage / Q000276:immunology; D006801:Humans; D007279:Injections, Subcutaneous; D020014:K562 Cells; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000637:transplantation; D008213:Lymphocyte Activation; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000556:secondary; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000276:immunology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000138:chemical synthesis / Q000276:immunology*; D015203:Reproducibility of Results; D012984:Software; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D058951:gp100 Melanoma Antigen
D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D006131:Growth Inhibitors; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C548637:PMEL protein, human; D010446:Peptide Fragments; C548642:Pmel protein, mouse; D058951:gp100 Melanoma Antigen