PMID: 3756906Nov 1, 1986Paper

Mechanism of antitumor activity in mice for anti-epidermal growth factor receptor monoclonal antibodies with different isotypes

Cancer Research
H MasuiJ Mendelsohn

Abstract

In previous studies of monoclonal antibodies (mAbs) against the receptor for epidermal growth factor (EGF) both 528 IgG2a and 225 IgG1 were shown to inhibit growth of A431 cell xenografts in athymic mice. The antitumor activities of the two mAbs were similar and, although they differ in their isotypes, they share many properties. The two mAbs bind to EGF receptors with identical affinities, compete with EGF for binding to EGF receptors, down regulate the receptors identically, block EGF-induced activation of tyrosine protein kinase activity to a comparable degree, and block EGF-induced changes in the proliferation of cultured cells. These similarities in physiological effects permit a direct comparison of the mechanisms of action mAbs of the IgG1 and IgG2a isotypes. We examined in vitro cytotoxicity against A431 cells, using 528 IgG2a and 225 IgG1 mAbs. 528 IgG2a, but not 225 IgG1, demonstrated partial complement-mediated cytotoxicity by the 51Cr release assay and by growth inhibition of cultured A431 cells. 528 IgG2a, but not 225 IgG1, was cytotoxic to A431 cells in the presence of activated peritoneal macrophages, as demonstrated by release of incorporated [3H]thymidine. Neither mAb showed any significant cytotoxicity to A431...Continue Reading

Related Concepts

Related Feeds

Antibody-Dependent Cell Cytotoxicity

Antibody-dependent cellular toxicity refers to the lysis of a target cell by a non-sensitized effector cell of the immune system as a result of antibodies binding to the target cell membrane and engaging the Fc receptors on the immune effector cells. Find the latest research on antibody-dependent cellular toxicity here.