Clinical and immunologic responses in melanoma patients vaccinated with MAGE-A3-genetically modified lymphocytes

Autor: Francesca Lunghi, Raffaella Greco, Vincenzo Russo, Annabella Di Florio, Corrado Gallo-Stampino, Giorgio Parmiani, Roberto Nicoletti, Santo Raffaele Mercuri, Monica Salomoni, Ferruccio Fazio, Pierre Coulie, Luigi Gianolli, Daniela Maggioni, Gianluigi Rigamonti, Raffaella Fontana, Roberto Crocchiolo, Matteo Del Fiacco, Lorenzo Pilla, Licia Rivoltini, Mario Santinami, Fabio Ciceri, Sylvain Mukenge, Catia Traversari, Roberto Patuzzo, Michele Maio, Marco Bregni, Claudio Bordignon, Antonio Lambiase, Alfonso Marchianò, Alessandro Del Maschio
Přispěvatelé: Russo, V, Pilla, L, Lunghi, F, Crocchiolo, R, Greco, R, Ciceri, Fabio, Maggioni, D, Fontana, R, Mukenge, S, Rivoltini, L, Rigamonti, G, Mercuri, Sr, Nicoletti, R, DEL MASCHIO, Alessandro, Gianolli, L, Fazio, F, Marchiano, A, Di Florio, A, Maio, M, Salomoni, M, Gallo-stampino, C, Del Fiacco, M, Lambiase, A, Coulie, Pg, Patuzzo, R, Parmiani, G, Traversari, C, Bordignon, Claudio, Santinami, M, Bregni, M.
Rok vydání: 2012
Předmět:
Zdroj: International journal of cancer (Online) 132 (2013): 2557–2566. doi:10.1002/ijc.27939
info:cnr-pdr/source/autori: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 Marchian; 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 Bordignon9,14, Mario Santinami16* and Marco Bregni3*/titolo:Clinical and immunologic responses in melanoma patients vaccinated with MAGE-A3-genetically modified lymphocytes./doi:10.1002%2Fijc.27939/rivista:International journal of cancer (Online)/anno:2013/pagina_da:2557/pagina_a:2566/intervallo_pagine:2557–2566/volume:132
ISSN: 1097-0215
Popis: 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. OI bregni, marco/0000-0002-3789-1199
Databáze: OpenAIRE
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