title: Cytokine-based gene therapy of human tumors. An overview.
abstract: This review first summarizes the different strategies of gene therapy of cancer and then focuses on the immunological approach. Several studies in animal models with cytokine gene-transduced tumor cells indicate that local cytokine release usually results in tumor growth inhibition. Moreover, in a number of cases vaccination with such cells can reduce growth of established tumors or even cure the tumor-bearing animals. Translation of such a principle in human clinical setting is reported. We have transduced human melanoma cells with genes coding for interleukin (IL)-2, IL-4 or B7-1 and characterized such lines. The phenotype did not change after gene insertion but the functional, immunostimulatory activity of IL-2 or B7-1 gene-transduced melanoma cells was significantly increased compared to that of parental lines. These-lines were then used to vaccinate melanoma patients. Preliminary results of trials with IL-2 gene-transduced cells are presented which indicate a weak clinical response and the activation of a melanoma-specific cytotoxic T lymphocyte response in a low percentage of patients.
authors.affiliation: Division of Experimental Oncology D, Instituto Nazionale Tumori, Milan, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Parmiani
authors.forename: F
authors.initials: F
authors.lastname: Arienti
authors.forename: J
authors.initials: J
authors.lastname: Sulé-Suso
authors.forename: C
authors.initials: C
authors.lastname: Melani
authors.forename: M P
authors.initials: MP
authors.lastname: Colombo
authors.forename: V
authors.initials: V
authors.lastname: Ramakrishna
authors.forename: F
authors.initials: F
authors.lastname: Belli
authors.forename: L
authors.initials: L
authors.lastname: Mascheroni
authors.forename: L
authors.initials: L
authors.lastname: Rivoltini
authors.forename: N
authors.initials: N
authors.lastname: Cascinelli
mesh_terms: D000818:Animals; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000235:genetics; D019496:Cancer Vaccines; D016207:Cytokines / Q000096:biosynthesis*; D015316:Genetic Therapy; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics; D008545:Melanoma / Q000276:immunology* / Q000628:therapy*; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D009374:Neoplasms, Experimental / Q000628:therapy; D011994:Recombinant Proteins / Q000096:biosynthesis; D014162:Transfection; D014407:Tumor Cells, Cultured; D014614:Vaccines, Synthetic
chemical_list: D018122:B7-1 Antigen; D019496:Cancer Vaccines; D016207:Cytokines; D007376:Interleukin-2; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D015847:Interleukin-4