Oncolytic Adenovirus Coding for Granulocyte Macrophage Colony-Stimulating Factor Induces Antitumoral Immunity in Cancer Patients
2010; American Association for Cancer Research; Volume: 70; Issue: 11 Linguagem: Inglês
10.1158/0008-5472.can-09-3567
ISSN1538-7445
AutoresVincenzo Cerullo, Sari Pesonen, Iulia Diaconu, Sophie Escutenaire, Petteri T. Arstila, Matteo Ugolini, Petri Nokisalmi, Mari Raki, Leena Laasonen, Merja Särkioja, Maria Rajecki, Lotta Kangasniemi, Kilian Guse, Andreas Helminen, Laura Ahtiainen, Ari Ristimäki, Anne Räisänen‐Sokolowski, Elina Haavisto, Minna Oksanen, Eerika Karli, Aila Karioja‐Kallio, Liisa Holm, Mauri Kouri, Timo Joensuu, Anna Kanerva, Akseli Hemminki,
Tópico(s)Viral gastroenteritis research and epidemiology
ResumoGranulocyte macrophage colony-stimulating factor (GMCSF) can mediate antitumor effects by recruiting natural killer cells and by induction of tumor-specific cytotoxic T-cells through antigen-presenting cells. Oncolytic tumor cell-killing can produce a potent costimulatory danger signal and release of tumor epitopes for antigen-presenting cell sampling. Therefore, an oncolytic adenovirus coding for GMCSF was engineered and shown to induce tumor-specific immunity in an immunocompetent syngeneic hamster model. Subsequently, 20 patients with advanced solid tumors refractory to standard therapies were treated with Ad5-D24-GMCSF. Of the 16 radiologically evaluable patients, 2 had complete responses, 1 had a minor response, and 5 had disease stabilization. Responses were frequently seen in injected and noninjected tumors. Treatment was well tolerated and resulted in the induction of both tumor-specific and virus-specific immunity as measured by ELISPOT and pentamer analysis. This is the first time that oncolytic virus-mediated antitumor immunity has been shown in humans. Ad5-D24-GMCSF is promising for further clinical testing.
Referência(s)