Oncolytic Adenovirus Coding for Granulocyte Macrophage Colony-Stimulating Factor Induces Antitumoral Immunity in Cancer Patients

被引：186

作者：

Cerullo, Vincenzo ^{[1
,2
,5
]}

Pesonen, Sari ^{[1
,2
,5
]}

Diaconu, Iulia ^{[1
,2
,5
]}

Escutenaire, Sophie ^{[1
,2
,5
]}

Arstila, Petteri T. ^{[3
]}

Ugolini, Matteo ^{[1
,2
,5
]}

Nokisalmi, Petri ^{[1
,2
,5
]}

Raki, Mari ^{[1
,2
,5
]}

Laasonen, Leena ^{[4
]}

Sarkioja, Merja ^{[1
,2
,5
]}

Rajecki, Maria ^{[1
,2
,5
]}

Kangasniemi, Lotta ^{[1
,2
,5
]}

Guse, Kilian ^{[1
,2
,5
]}

Helminen, Andreas ^{[1
,2
,5
,9
]}

Ahtiainen, Laura ^{[1
,2
,5
]}

Ristimaki, Ari ^{[5
,6
,8
]}

Raisanen-Sokolowski, Anne ^{[5
]}

Haavisto, Elina ^{[1
,2
,5
]}

Oksanen, Minna ^{[1
,2
,5
]}

Karli, Eerika ^{[1
,2
,5
]}

Karioja-Kallio, Aila ^{[1
,2
,5
]}

Holm, Sirkka-Liisa ^{[1
,2
,5
]}

Kouri, Mauri ^{[9
]}

Joensuu, Timo ^{[9
]}

Kanerva, Anna ^{[1
,2
,7
]}

Hemminki, Akseli ^{[1
,2
,5
]}

机构：

[1] Univ Helsinki, Transplantat Lab, Canc Gene Therapy Grp, Haartman Inst, FIN-00014 Helsinki, Finland

[2] Univ Helsinki, Finnish Inst Mol Med, FIN-00014 Helsinki, Finland

[3] Univ Helsinki, Dept Bacteriol & Immunol, Haartman Inst, FIN-00014 Helsinki, Finland

[4] Univ Helsinki, Helsinki Med Imaging Ctr, FIN-00014 Helsinki, Finland

[5] Univ Helsinki, Cent Hosp, HUSLAB, FIN-00014 Helsinki, Finland

[6] Univ Helsinki, Cent Hosp, Dept Pathol, FIN-00014 Helsinki, Finland

[7] Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, FIN-00014 Helsinki, Finland

[8] Biomedicum Helsinki, Genome Scale Biol Program, Helsinki, Finland

[9] Int Comprehens Canc Ctr Docrates, Helsinki, Finland

来源：

CANCER RESEARCH | 2010年 / 70卷 / 11期

关键词：

PHASE-I TRIAL; CELL LUNG-CANCER; GM-CSF; OVARIAN-CANCER; REPLICATING ADENOVIRUS; RESPONSE CRITERIA; DENDRITIC CELLS; GENE-TRANSFER; NECK-CANCER; T-CELLS;

D O I：

10.1158/0008-5472.CAN-09-3567

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Granulocyte 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. Cancer Res; 70(11); 4297-309. (C) 2010 AACR.

引用

页码：4297 / 4309

页数：13

共 49 条

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