title: Serotype chimeric oncolytic adenovirus coding for GM-CSF for treatment of sarcoma in rodents and humans.
abstract: 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.
authors.affiliation: Cancer Gene Therapy Group Department of Pathology and Transplantation Laboratory, Haartman Institute, University of Helsinki, Helsinki, Finland.
authors.forename: Simona
authors.initials: S
authors.lastname: Bramante
authors.forename: Anniina
authors.initials: A
authors.lastname: Koski
authors.forename: Anja
authors.initials: A
authors.lastname: Kipar
authors.forename: Iulia
authors.initials: I
authors.lastname: Diaconu
authors.forename: Ilkka
authors.initials: I
authors.lastname: Liikanen
authors.forename: Otto
authors.initials: O
authors.lastname: Hemminki
authors.forename: Lotta
authors.initials: L
authors.lastname: Vassilev
authors.forename: Suvi
authors.initials: S
authors.lastname: Parviainen
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cerullo
authors.forename: Saila K
authors.initials: SK
authors.lastname: Pesonen
authors.forename: Minna
authors.initials: M
authors.lastname: Oksanen
authors.forename: Raita
authors.initials: R
authors.lastname: Heiskanen
authors.forename: Noora
authors.initials: N
authors.lastname: Rouvinen-Lagerström
authors.forename: Maiju
authors.initials: M
authors.lastname: Merisalo-Soikkeli
authors.forename: Tiina
authors.initials: T
authors.lastname: Hakonen
authors.forename: Timo
authors.initials: T
authors.lastname: Joensuu
authors.forename: Anna
authors.initials: A
authors.lastname: Kanerva
authors.forename: Sari
authors.initials: S
authors.lastname: Pesonen
authors.forename: Akseli
authors.initials: A
authors.lastname: Hemminki
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D005260:Female; D015316:Genetic Therapy; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D015552:Injections, Intralesional; D008647:Mesocricetus; D051379:Mice; D008819:Mice, Nude; D050130:Oncolytic Virotherapy; D011379:Prognosis; D012509:Sarcoma / Q000097:blood / Q000401:mortality / Q000628:therapy*; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D014779:Virus Replication; D023041:Xenograft Model Antitumor Assays
chemical_list: D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: GM-CSF; animal models of cancer; cancer gene therapy; oncolytic adenovirus; sarcoma