TY - JOUR
T1 - Clinical and immunologic responses in melanoma patients vaccinated with MAGE-A3-genetically modified lymphocytes
AU - Russo, Vincenzo
AU - Pilla, Lorenzo
AU - Lunghi, Francesca
AU - Crocchiolo, Roberto
AU - Greco, Raffaella
AU - Ciceri, Fabio
AU - Maggioni, Daniela
AU - Fontana, Raffaella
AU - Mukenge, Sylvain
AU - Rivoltini, Licia
AU - Rigamonti, Gianluigi
AU - Mercuri, Santo Raffaele
AU - Nicoletti, Roberto
AU - Del Maschio, Alessandro
AU - Gianolli, Luigi
AU - Fazio, Ferruccio
AU - Marchianò, Alfonso
AU - Di Florio, Annabella
AU - Maio, Michele
AU - Salomoni, Monica
AU - Gallo-Stampino, Corrado
AU - Del Fiacco, Matteo
AU - Lambiase, Antonio
AU - Coulie, Pierre G.
AU - Patuzzo, Roberto
AU - Parmiani, Giorgio
AU - Traversari, Catia
AU - Bordignon, Claudio
AU - Santinami, Mario
AU - Bregni, Marco
PY - 2013/6/1
Y1 - 2013/6/1
N2 - 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.
AB - 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.
KW - active immunotherapy
KW - antigen-specific immune responses
KW - melanoma
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U2 - 10.1002/ijc.27939
DO - 10.1002/ijc.27939
M3 - Article
C2 - 23151995
AN - SCOPUS:84875596876
VL - 132
SP - 2557
EP - 2566
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 11
ER -