title: Intralesional adenovirus-mediated interleukin-2 gene transfer for advanced solid cancers and melanoma.
abstract: Numerous preclinical and clinical studies have shown that interleukin-2 (IL-2) induces regression of metastatic tumors. We have conducted a phase I/II, multicenter, open-label, dose-escalating study to evaluate the safety, efficacy, and biological effects of repeated intratumoral injections of adenovirus-IL-2 (TG1024) in patients with advanced solid tumors and melanoma. Thirty five patients (twenty-five with metastatic melanoma and ten with other solid tumors) were treated in eight successive cohorts at dose levels ranging from 3 x 10(8) to 3 x 10(11) viral particles (vp). Intratumoral TG1024 injections in combination with dacarbazine (DTIC) were tested in metastatic melanoma in one cohort. No clinical responses were observed at doses below 3 x 10(11) vp. Six local objective responses were recorded in patients receiving 3 x 10(11) vp per treatment [five in metastatic melanoma and one in metastatic squamous cell carcinoma (SCC) of the skin], of which two were complete responses (CRs). Most of the common side effects were injection site reactions and flu-like syndrome. TG1024 dose intensification across cohorts resulted in increased serum IL-2 levels after the injection. Intratumoral TG1024 injection induced pronounced inflammation of the treated lesion, with predominant CD8(+), TIA+ lymphocytic infiltrate. Our results show that intratumoral injections of TG1024 are safe and well tolerated. The clinical activity of TG1024 observed in this study warrants further investigations.
authors.affiliation: Department of Dermatology, University Hospital Zurich, Zurich, Switzerland. reinhard.dummer@usz.ch
authors.forename: Reinhard
authors.initials: R
authors.lastname: Dummer
authors.forename: Christoph
authors.initials: C
authors.lastname: Rochlitz
authors.forename: Thierry
authors.initials: T
authors.lastname: Velu
authors.forename: Bruce
authors.initials: B
authors.lastname: Acres
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Limacher
authors.forename: Pascal
authors.initials: P
authors.lastname: Bleuzen
authors.forename: Gisèle
authors.initials: G
authors.lastname: Lacoste
authors.forename: Philippe
authors.initials: P
authors.lastname: Slos
authors.forename: Pedro
authors.initials: P
authors.lastname: Romero
authors.forename: Mirjana
authors.initials: M
authors.lastname: Urosevic
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000628:therapy; D003606:Dacarbazine / Q000494:pharmacology*; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000628:therapy*; D008875:Middle Aged; D009362:Neoplasm Metastasis
chemical_list: D007376:Interleukin-2; D003606:Dacarbazine