Clinical and immunological evaluation of patients with metastatic melanoma undergoing immunization with the HLA-Cw*0702-associated epitope MAGE-A12:170-178.

Abstract

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.

• Authors: Maria P Bettinotti, Monica C Panelli, Erin Ruppe, Simone Mocellin, Giao Q Phan, Donald E White, Francesco M Marincola
• Journal: International journal of cancer (Int J Cancer) Vol. 105 Issue 2 Pg. 210-6 (Jun 10 2003) ISSN: 0020-7136 [Print] United States
• PMID: 12673681 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial)
• Copyright: Copyright 2003 Wiley-Liss, Inc.

Chemical References

• Antibodies, Monoclonal
• Antigens, Neoplasm
• Cancer Vaccines
• DNA Primers
• HLA-C Antigens
• MAGEA12 protein, human
• Neoplasm Proteins
• Peptide Fragments
• RNA, Messenger
• Interferon-gamma

Topics

• Adult
• Aged
• Antibodies, Monoclonal
• Antigens, Neoplasm (genetics, immunology)
• Cancer Vaccines (therapeutic use)
• Case-Control Studies
• Cells, Cultured
• DNA Primers (chemistry)
• Female
• HLA-C Antigens (immunology)
• Humans
• Immunity, Cellular
• Immunization
• Immunotherapy
• Interferon-gamma (genetics)
• Male
• Melanoma (genetics, immunology, secondary, therapy)
• Middle Aged
• Neoplasm Proteins (genetics, immunology)
• Peptide Fragments (genetics, immunology)
• RNA, Messenger (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Skin Neoplasms (genetics, immunology, pathology, therapy)
• T-Lymphocytes, Cytotoxic (immunology, metabolism)
• Treatment Outcome