Document Detail

Clinical and immunologic responses in melanoma patients vaccinated with MAGE-A3-genetically modified lymphocytes.
MedLine Citation:
PMID:  23151995     Owner:  NLM     Status:  MEDLINE    
Cancer vaccines have recently been shown to induce some clinical benefits. The relationship between clinical activity and anti-vaccine T cell responses is somewhat controversial. Indeed, in many trials it has been documented that the induction of vaccine-specific T cells exceeds the clinical responses observed. Here, we evaluate immunological and clinical responses in 23 MAGE-A3(+) melanoma patients treated with autologous lymphocytes genetically engineered to express the tumor antigen MAGE-A3 and the viral gene product thymidine kinase of the herpes simplex virus (HSV-TK). HSV-TK was used as safety system in case of adverse events and as tracer antigen to monitor the immune competence of treated patients. The increase of anti-TK and anti-MAGE-A3 T-cells after vaccination was observed in 90 and 27% of patients, respectively. Among 19 patients with measurable disease, we observed a disease control rate of 26.3%, with one objective clinical response, and four durable, stable diseases. Three patients out of five with no evidence of disease (NED) at the time of vaccination remained NED after 73+, 70+ and 50+ months. Notably, we report that only patients experiencing MAGE-A3-specific immune responses showed a clinical benefit. Additionally, we report that responder and non-responder patients activate and expand T cells against the tracer antigen TK in a similar way, suggesting that local rather than systemic immune suppression might be involved in limiting clinically relevant antitumor immune responses.
Vincenzo Russo; Lorenzo Pilla; Francesca Lunghi; Roberto Crocchiolo; Raffaella Greco; Fabio Ciceri; Daniela Maggioni; Raffaella Fontana; Sylvain Mukenge; Licia Rivoltini; Gianluigi Rigamonti; Santo Raffaele Mercuri; Roberto Nicoletti; Alessandro Del Maschio; Luigi Gianolli; Ferruccio Fazio; Alfonso Marchianò; Annabella Di Florio; Michele Maio; Monica Salomoni; Corrado Gallo-Stampino; Matteo Del Fiacco; Antonio Lambiase; Pierre G Coulie; Roberto Patuzzo; Giorgio Parmiani; Catia Traversari; Claudio Bordignon; Mario Santinami; Marco Bregni
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-12-13
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  132     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-03-26     Completed Date:  2013-05-28     Revised Date:  2013-08-28    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2557-66     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 UICC.
Division of Molecular Oncology, Unit of Cancer Gene Therapy, Program in Immunology and Bio Immunotherapy and Gene Therapy of Cancer, San Raffaele Scientific Institute, Milan, Italy.
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MeSH Terms
Antigens, Neoplasm / immunology*
Bone Neoplasms / immunology,  mortality,  therapy
Cancer Vaccines / therapeutic use*
Clinical Trials, Phase II as Topic
Follow-Up Studies
Genetic Therapy*
Hypersensitivity, Delayed
Liver Neoplasms / immunology,  mortality,  therapy
Lung Neoplasms / immunology,  mortality,  therapy
Melanoma / immunology*,  mortality,  therapy
Middle Aged
Neoplasm Proteins / immunology*
Neoplasm Staging
Skin Neoplasms / immunology,  mortality,  therapy
T-Lymphocytes / immunology*,  metabolism
Thymidine Kinase / immunology,  metabolism
Reg. No./Substance:
0/Antigens, Neoplasm; 0/Cancer Vaccines; 0/MAGEA3 protein, human; 0/Neoplasm Proteins; EC Kinase
Comment In:
Immunotherapy. 2013 Jul;5(7):691-4   [PMID:  23829619 ]

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