Clinical and immunological evaluation of patients with metastatic melanoma undergoing immunization with the HLA‐Cw0702‐associated epitope MAGE‐A12:170–178

• Published in: International journal of cancer 2003-06, Vol.105 (2), p.210-216
• Main Authors: Bettinotti, Maria P., Panelli, Monica C., Ruppe, Erin, Mocellin, Simone, Phan, Giao Q., White, Donald E., Marincola, Francesco M.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antibodies, Monoclonal; Antigens, Neoplasm - genetics; Antigens, Neoplasm - immunology; Antineoplastic agents; Biological and medical sciences; Cancer Vaccines - therapeutic use; Case-Control Studies; Cells, Cultured; DNA Primers - chemistry; Female; HLA-C Antigens - immunology; Humans; immune response; Immunity, Cellular; Immunization; Immunotherapy; Interferon-gamma - genetics; MAGE; Male; Medical sciences; melanoma; Melanoma - genetics; Melanoma - immunology; Melanoma - secondary; Melanoma - therapy; Middle Aged; Neoplasm Proteins - genetics; Neoplasm Proteins - immunology; Peptide Fragments - genetics; Peptide Fragments - immunology; Pharmacology. Drug treatments; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; Skin Neoplasms - genetics; Skin Neoplasms - immunology; Skin Neoplasms - pathology; Skin Neoplasms - therapy; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Cytotoxic - metabolism; Treatment Outcome
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.11045

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‐γ 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. © 2003 Wiley‐Liss, Inc.