Combination Therapy with Antibody and Interleukin–2 Gene Transfer against Multidrug–resistant Cancer Cells

In the present study, we examined the effect of intcrlcukin–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 G418resistant 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–positlve tumors, IL2–AD10 cells were cotransplanted 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 jag/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.