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

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 SalomoniCorrado Gallo-Stampino, Matteo Del Fiacco, Antonio Lambiase, Pierre G. Coulie, Roberto Patuzzo, Giorgio Parmiani, Catia Traversari, Claudio Bordignon, Mario Santinami, Marco Bregni

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)2557-2566
Number of pages10
JournalInternational Journal of Cancer
Volume132
Issue number11
DOIs
Publication statusPublished - Jun 1 2013

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Keywords

  • active immunotherapy
  • antigen-specific immune responses
  • melanoma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Russo, V., Pilla, L., Lunghi, F., Crocchiolo, R., Greco, R., Ciceri, F., Maggioni, D., Fontana, R., Mukenge, S., Rivoltini, L., Rigamonti, G., Mercuri, S. R., Nicoletti, R., Del Maschio, A., Gianolli, L., Fazio, F., Marchianò, A., Di Florio, A., Maio, M., ... Bregni, M. (2013). Clinical and immunologic responses in melanoma patients vaccinated with MAGE-A3-genetically modified lymphocytes. International Journal of Cancer, 132(11), 2557-2566. https://doi.org/10.1002/ijc.27939