Combination therapy with antibody and interleukin-2 gene transfer against multidrug-resistant cancer cells

Tsutomu Shinohara, Yoshikazu Sugimoto, Shigeo Sato, Saburo Sone, Takashi Tsuruo

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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 μg/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.

Original languageEnglish
Pages (from-to)1100-1107
Number of pages8
JournalJapanese Journal of Cancer Research
Volume88
Issue number11
DOIs
Publication statusPublished - 1997 Nov

Keywords

  • Antibody-dependent cell-mediated cytotoxicity
  • Interleukin-2
  • Internal ribosome entry site
  • Multidrug resistance
  • Natural killer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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