Cytokine-based gene therapy of human tumors. An overview.
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.
Parmiani
G
G
Division of Experimental Oncology D, Instituto Nazionale Tumori, Milan, Italy.
Arienti
F
F
Sulé-Suso
J
J
Melani
C
C
Colombo
M P
MP
Ramakrishna
V
V
Belli
F
F
Mascheroni
L
L
Rivoltini
L
L
Cascinelli
N
N
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
D018122:B7-1 Antigen; D019496:Cancer Vaccines; D016207:Cytokines; D007376:Interleukin-2; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D015847:Interleukin-4