Combination therapy with antibody and interleukin-2 gene transfer against multidrug-resistant cancer cells.
In the present study, we examined the effect of interleukin-2 (IL-2) gene transfer into multidrug resistance (MDR) cancer cells on the therapeutic efficacy of MRK16. Human MDR ovarian cancer cells, AD10, were transduced with a bicistronic IL-2 retrovirus, Ha-IL2-IRES-Neo. The G418-resistant population, IL2-AD10, secreted IL-2 into the culture supernatant and did not form a tumor mass in nude mice. The IL2-AD10 cells were more susceptible to the cytotoxicity of murine spleen cells than AD10 cells in vitro. For examination of the effect of IL-2 gene transfer on the antitumor activity of MRK16 against P-glycoprotein-positive tumors, IL2-AD10 cells were co-transplanted s.c. with AD10 cells into nude mice in a ratio of 1:3, and the mice were treated with MRK16 on days 2 and 7. MRK16 markedly inhibited the growth of AD10 cells mixed with IL2-AD10 cells under conditions (0.3-1 microgram/body) where it showed only marginal effects on the growth of AD10 tumors. These findings suggest that IL-2 gene transfer potentiates the antitumor activity of MRK16 against MDR tumors.
Shinohara
T
T
Cancer Chemotherapy Center, Japanes Foundation for Cancer Research, Tokyo.
Sugimoto
Y
Y
Sato
S
S
Sone
S
S
Tsuruo
T
T
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D018014:Gene Transfer Techniques; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics* / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D004317:Doxorubicin