title: Clinical phase I intratumoral administration of two recombinant ALVAC canarypox viruses expressing human granulocyte-macrophage colony-stimulating factor or interleukin-2: the transgene determines the composition of the inflammatory infiltrate.
abstract: Immunotherapy employs cytokines for modifying local inflammatory reactions. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to activate dendritic cells, macrophages, and granulocytes leading to clinical trials using GM-CSF-based cancer vaccine approaches. Interleukin-2 (IL-2) is an important T cell stimulatory cytokine approved as exogenous antitumor agent. The ALVAC viral vector system uses a recombinant canarypox virus for local gene expression. We report a phase I clinical trial using intratumoral administration of ALVAC GM-CSF or ALVAC IL-2 in skin metastases of melanoma or leiomyosarcoma. ALVAC GM-CSF and ALVAC IL-2 were injected at 107.12 and 106.92, 50% cell culture infectious dose in eight metastases with acceptable tolerability. Local and systemic inflammatory reactions were observed. The transgene determined the local infiltrate: GM-CSF induced monocyte and macrophage enrichment of the peritumoral inflammatory infiltrate, whereas IL-2 increased local T lymphocytes. Stable disease of injected lesions was seen after ALVAC GM-CSF application, whereas ALVAC IL-2 treatment led to partial regression in three out of eight injected tumors, accompanied by decreased expression of melanocytic antigens. Local GM-CSF expression could be induced. In summary, ALVAC GM-CSF and ALVAC IL-2 injections are safe and can mediate local biologic and immunologic effects.
authors.affiliation: Department of Dermatology, University Hospital Zürich, Zürich, Switzerland. gfl@hofbauer.ch
authors.forename: Günther F L
authors.initials: GF
authors.lastname: Hofbauer
authors.forename: Tobias
authors.initials: T
authors.lastname: Baur
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Bonnet
authors.forename: Eric
authors.initials: E
authors.lastname: Tartour
authors.forename: Günter
authors.initials: G
authors.lastname: Burg
authors.forename: Neil L
authors.initials: NL
authors.lastname: Berinstein
authors.forename: Reinhard
authors.initials: R
authors.lastname: Dummer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D006801:Humans; D007167:Immunotherapy; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D007890:Leiomyosarcoma / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D008264:Macrophages / Q000276:immunology; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000473:pathology / Q000556:secondary* / Q000628:therapy*; D008875:Middle Aged; D011994:Recombinant Proteins; D012878:Skin Neoplasms / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019076:Transgenes; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use
chemical_list: C078788:ALVAC vaccine; D019496:Cancer Vaccines; D007376:Interleukin-2; D011994:Recombinant Proteins; D014765:Viral Vaccines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor