PMID: 9435865Jan 22, 1998Paper

Lysis of murine B lymphoma cells by transgenic phagocytes via a human Fc gamma RI x murine MHC class II bispecific antibody

Cancer Immunology, Immunotherapy : CII
I A HeijnenJ G van de Winkel

Abstract

The class I IgG receptor (Fc gamma RI) on cytotoxic effector cells has been reported to initiate destruction of tumour cells by effector cells in vitro. We are aiming at developing an immunocompetent model to evaluate the cytotoxic capacity of human Fc gamma RI for the rejection of tumour cells in vivo. Therefore, we recently generated a transgenic mouse strain expressing human Fc gamma RI on monocytes, macrophages, and neutrophils. In these mice, the human receptor is up-regulated by granulocyte-colony-stimulating factor (G-CSF) and is able to trigger cellular responses. Subsequently, in the present study the B cell lymphoma IIA1.6 cell line is selected as a tumour target, and a human Fc gamma RI-directed antitumour bispecific antibody (bsAb) is constructed and characterized. Fab' fragments of mAb 22, which bind hFc gamma RI at an epitope that is distinct from the ligand binding site, were chemically linked to Fab' fragments of rat anti-(mMHC class II antigens) mAb M5/114, yielding bsAb 22 x M5/114. This bsAb was able to bind simultaneously to hFc gamma RI and mMHC class II antigens in a dose-dependent fashion. Binding of 22 x M5/114 to Fc gamma RI was not inhibited in the presence of human IgG. It is important to note that, M...Continue Reading

Citations

Oct 2, 2001·Critical Reviews in Oncology/hematology·P M McLaughlinL F de Leij
Mar 15, 2012·Lasers in Medical Science·Farahnaz FahimipourArash Khojasteh
Sep 29, 2020·Frontiers in Immunology·Charita FurumayaHanke L Matlung
Feb 9, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Shimpei KasagiShunichi Kumagai

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