Details

Autor(en) / Beteiligte

• Bramante, Simona
• Koski, Anniina
• Kipar, Anja
• Diaconu, Iulia
• Liikanen, Ilkka
• Hemminki, Otto
• Vassilev, Lotta
• Parviainen, Suvi
• Cerullo, Vincenzo
• Pesonen, Saila K
• Oksanen, Minna
• Heiskanen, Raita
• Rouvinen‐Lagerström, Noora
• Merisalo‐Soikkeli, Maiju
• Hakonen, Tiina
• Joensuu, Timo
• Kanerva, Anna
• Pesonen, Sari
• Hemminki, Akseli

Titel

Serotype chimeric oncolytic adenovirus coding for GM‐CSF for treatment of sarcoma in rodents and humans

Ist Teil von

• International journal of cancer, 2014-08, Vol.135 (3), p.720-730

Ort / Verlag

Hoboken, NJ: Wiley-Blackwell

Erscheinungsjahr

2014

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• Sarcomas are a relatively rare cancer, but often incurable at the late metastatic stage. Oncolytic immunotherapy has gained attention over the past years, and a wide range of oncolytic viruses have been delivered via intratumoral injection with positive safety and promising efficacy data. Here, we report preclinical and clinical results from treatment of sarcoma with oncolytic adenovirus Ad5/3‐D24‐GMCSF (CGTG‐102). Ad5/3‐D24‐GMCSF is a serotype chimeric oncolytic adenovirus coding for human granulocyte‐macrophage colony‐stimulating factor (GM‐CSF). The efficacy of Ad5/3‐D24‐GMCSF was evaluated on a panel of soft‐tissue sarcoma (STS) cell lines and in two animal models. Sarcoma specific human data were also collected from the Advanced Therapy Access Program (ATAP), in preparation for further clinical development. Efficacy was seen in both in vitro and in vivo STS models. Fifteen patients with treatment‐refractory STS (13/15) or primary bone sarcoma (2/15) were treated in ATAP, and treatments appeared safe and well‐tolerated. A total of 12 radiological RECIST response evaluations were performed, and two cases of minor response, six cases of stable disease and four cases of progressive disease were detected in patients progressing prior to virus treatment. Overall, the median survival time post treatment was 170 days. One patient is still alive at 1,459 days post virus treatment. In summary, Ad5/3‐D24‐GMCSF appears promising for the treatment of advanced STS; a clinical trial for treatment of refractory injectable solid tumors including STS is ongoing.© 2013 UICC What's new? Oncolytic viruses are a promising treatment strategy against cancer. They can also be used as gene‐therapy vectors, to further stimulate the antitumor immune response. In this study, the authors evaluated an adenovirus carrying the gene for GM‐CSF, with positive results in animal models of soft‐tissue sarcoma (STS). The study also demonstrated that the virus can spread to non‐injected tumors, suggesting that it might be useful for the treatment of metastatic disease. Furthermore, the treatment was well‐tolerated in human sarcoma patients, with evidence of antitumor efficacy, supporting further clinical trials.