Cancer Chemotherapy and Pharmacology

, Volume 38, Issue 4, pp 303–308

Epidermal growth factor receptor-dependent cytotoxic effect by an EGF—ribonuclease conjugate on human cancer cell lines -A trial for less immunogenic chimeric toxin-

-A trial for less immunogenic chimeric toxin-
  • Hiromitsu Jinno
  • M. Ueda
  • Soji Ozawa
  • Kiyoshi Kikuchi
  • Tadashi Ikeda
  • Koji Enomoto
  • Masaki Kitajima
ORIGINAL ARTICLE

DOI: 10.1007/s002800050487

Cite this article as:
Jinno, H., Ueda, M., Ozawa, S. et al. Cancer Chemother Pharmacol (1996) 38: 303. doi:10.1007/s002800050487

Abstract

 Mammalian pancreatic ribonuclease (RNase) was conjugated chemically via a disulfide bond to human or murine epidermal growth factor (EGF). The conjugation between EGF and RNase was ascertained by SDS-PAGE using reduced and nonreduced conjugates. The EGF–RNase conjugate retained potent RNase activity and competed with 125I-EGF for binding to EGFR to the same extent as unconjugated EGF. Both the human and murine EGF–RNase conjugates showed dose-dependent cytotoxicity against EGFR- overexpressing A431 human squamous carcinoma cells with IC50 values of 3×10-7M and 6×10-7M, respectively, whereas free RNase had an IC50 of 10-4M. Against the EGFR-deficient small-cell lung cancer cell line H69, the EGF–RNase conjugate had no cytotoxic effect. The Human EGF–RNase conjugate showed dose-dependent cytotoxicity against other squamous carcinoma cell lines (TE-5, TE-1) and breast cancer cell lines (BT-20, SK-BR-3, MCF-7) and the cytotoxicity of the conjugate correlated positively with the level of expression of EGFR by each cell line. An unconjugated mixture of EGF and RNase had no greater effect than RNase alone on any cell line. Excess free EGF blocked EGF–RNase conjugate cytotoxicity against A431 cells. These results suggest that the EGF–RNase conjugate may be a more effective anticancer agent with less immunogenicity than coventional chimeric toxins.

Key words EGFRibonucleaseConjugateBreast cancerEsophageal cancer

Copyright information

© Springer-Verlag Berlin Heidelberg 1996

Authors and Affiliations

  • Hiromitsu Jinno
    • 1
  • M. Ueda
    • 1
  • Soji Ozawa
    • 1
  • Kiyoshi Kikuchi
    • 1
  • Tadashi Ikeda
    • 1
  • Koji Enomoto
    • 1
  • Masaki Kitajima
    • 1
  1. 1.Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160, Japan Fax: 81-3–3355–4707JP