Oncolytic adenovirus coding for granulocyte macrophage colony-stimulating factor induces antitumoral immunity in cancer patients.
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.
Cerullo
Vincenzo
V
Cancer Gene Therapy Group, Transplantation Laboratory, Haartman Institute and Finnish Institute of Molecular Medicine, Department of Bacteriology and Immunology, Haartman Institute, Helsinki Medical Imaging Center, University of Helsinki, Helsinki, Finland.
Pesonen
Sari
S
Diaconu
Iulia
I
Escutenaire
Sophie
S
Arstila
Petteri T
PT
Ugolini
Matteo
M
Nokisalmi
Petri
P
Raki
Mari
M
Laasonen
Leena
L
Särkioja
Merja
M
Rajecki
Maria
M
Kangasniemi
Lotta
L
Guse
Kilian
K
Helminen
Andreas
A
Ahtiainen
Laura
L
Ristimäki
Ari
A
Räisänen-Sokolowski
Anne
A
Haavisto
Elina
E
Oksanen
Minna
M
Karli
Eerika
E
Karioja-Kallio
Aila
A
Holm
Sirkka-Liisa
SL
Kouri
Mauri
M
Joensuu
Timo
T
Kanerva
Anna
A
Hemminki
Akseli
A
D000256:Adenoviridae / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D000818:Animals; D006224:Cricetinae; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D016179:Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000276:immunology; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy* / Q000821:virology; D050130:Oncolytic Virotherapy / Q000379:methods*; D000077022:Survivin; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection
C107489:BIRC5 protein, human; D018984:Epitopes, T-Lymphocyte; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D000077022:Survivin; D016179:Granulocyte Colony-Stimulating Factor