Clinical and immunological evaluation of patients with metastatic melanoma undergoing immunization with the HLA-Cw*0702-associated epitope MAGE-A12:170-178.
Patients with metastatic melanoma who expressed HLA-Cw*0702 and whose tumors had demonstrable MAGE-A12 expression were immunized with the peptide MAGE-A12:170-178 administered subcutaneously in incomplete Freund's adjuvant (IFA). The peptide was administered either every week or every 3 weeks for 4 cycles. Patients were evaluated for toxicity and for immunologic and clinical response to peptide immunization. Pre-treatment fine needle aspirates were obtained to document MAGE-A12 expression for enrollment. MAGE-A12 mRNA was identified in 62% of specimens. Nine patients were selected for vaccination based on MAGE-A12 expression and the presence of HLA-Cw*0702. The immune response was monitored both by tetrameric HLA-Cw*0702/MAGE-A12:170-178 complexes and by analysis of interferon-gamma mRNA transcription using a quantitative real-time polymerase chain reaction assay after peptide-specific stimulation. The samples consisted of circulating lymphocytes analyzed ex vivo or after 10 to 14 days of in vitro sensitization. One of 9 patients sustained an ongoing partial clinical response. No convincing evidence of enhancement of the systemic immune response against MAGE-A12:170-178 could be documented. Because of the modest immunological and clinical results, the present protocol has been discontinued as new routes of administration are being considered.
Bettinotti
Maria P
MP
Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA.
Panelli
Monica C
MC
Ruppe
Erin
E
Mocellin
Simone
S
Phan
Giao Q
GQ
White
Donald E
DE
Marincola
Francesco M
FM
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D019496:Cancer Vaccines / Q000627:therapeutic use*; D016022:Case-Control Studies; D002478:Cells, Cultured; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D015236:HLA-C Antigens / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007114:Immunization; D007167:Immunotherapy; D007371:Interferon-gamma / Q000235:genetics; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000276:immunology* / Q000556:secondary / Q000628:therapy; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology*; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism*; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D017931:DNA Primers; D015236:HLA-C Antigens; C409589:MAGEA12 protein, human; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D012333:RNA, Messenger; D007371:Interferon-gamma