Individualized synthetic peptide vaccines with GM-CSF in locally advanced melanoma patients.
We report on 10 patients with resected American Joint Committee on Cancer (AJCC)stage IIA-IIIC melanoma receiving individualized adjuvant peptide vaccinations derived from the melanosomal antigens MelanA/MART1, gp100 and tyrosinase, according to patient tumor associated HLA restricted antigen expression, in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF). Except for 1 patient, all patients had received systemic pretreatment with immunotherapy (n = 8), chemoimmunotherapy (n = 1), chemotherapy (n = 1), or cefalectin therapy (n = 1). Upon prior therapy, 7 of 10 patients had progressed with subcutaneous/cutaneous (n = 2), lymph node (n = 3), or subcutaneous/cutaneous and lymph node (n = 2)metastases, which were subsequently resected prior to vaccination. After a mean of 6.5 vaccination cycles, progression-free survival was 6 months (median, range 2-10). Five patients were relapse-free for 1+ up to 21+ months, 3 patients developed a solitary cutaneous metastasis, and 2 patients developed multiple metastases during vaccination. Overall, vaccine treatment was well tolerated, with no severe side-effects. Eight of 10 patients developed local delayed type hypersensitivity (DTH)reactions to synthetic peptides after the first or second injection. In 2 patients, transient fever, nausea, diarrhea, and muscle pain of National Cancer Institute (NCI)Grade I occurred. In summary, individualized synthetic peptide vaccination, combined with GM-CSF, was feasible and warrants further clinical investigation.
Atzpodien
Jens
J
Fachklinik Hornheide an der Universität Münster, Münster, Germany. SekrProfAtzpodien@yahoo.de
Fluck
Michael
M
Reitz
Martina
M
D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D006680:HLA Antigens / Q000378:metabolism; D006801:Humans; D008198:Lymph Nodes; D008207:Lymphatic Metastasis; D058965:MART-1 Antigen; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008562:Membrane Glycoproteins / Q000276:immunology; D008875:Middle Aged; D014442:Monophenol Monooxygenase / Q000276:immunology; D009363:Neoplasm Proteins / Q000276:immunology; D009367:Neoplasm Staging; D010446:Peptide Fragments / Q000276:immunology* / Q000627:therapeutic use; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D014611:Vaccination; D058951:gp100 Melanoma Antigen
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D006680:HLA Antigens; D058965:MART-1 Antigen; C548667:MLANA protein, human; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C548637:PMEL protein, human; D010446:Peptide Fragments; D058951:gp100 Melanoma Antigen; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D014442:Monophenol Monooxygenase