Modulation of drug-induced cytotoxicity by a bispecific monoclonal antibody that recognizes the epidermal growth factor receptor and doxorubicin

Daniele Morelli, Alessandro Sardini, Elena Villa, Maria Luisa Villa, Sylvie Ménard, Maria I. Colnaghi, Andrea Balsari

Research output: Contribution to journalArticle

Abstract

A hybrid hybridoma secreting a bispecific hybrid mAb (bsmAb), which recognizes both the epidermal growth factor receptor (EGF-R) and the drug doxorubicin, was produced by somatic hybridization of two hybridomas. The bsmAb obtained was able to retarget doxorubicin cytotoxicity in vitro specifically on EGF-R-positive cells exerting at the same time an antidotal effect on cells that did not overexpress the EGF-R. Distribution studies in mice indicate that the bsmAb selectively delivers the drug to tumour cells and modifies doxorubicin biodistribution with a statistically significant decrease of drug concentration in the intestine, which is the main target of early anthracycline toxicity. In keeping with this finding is the remarkable antidotal activity exerted by bsmAb in mice treated with doxorubiein, which is proved by retardation in loss of body weight and mortality. The effectiveness on tumour growth of the mAb followed by the administration of doxorubicin appears to be equal to that of the drug alone; however, the bsmAb exerts a remarkable antidotal activity.

Original languageEnglish
Pages (from-to)171-177
Number of pages7
JournalCancer Immunology, Immunotherapy
Volume38
Issue number3
DOIs
Publication statusPublished - May 1994

Keywords

  • Antidotal activity
  • Bispecific monoclonal antibody
  • Doxorubicin
  • EGF receptor
  • Immuno-modulation

ASJC Scopus subject areas

  • Oncology
  • Immunology
  • Cancer Research

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