An IgG1-like bispecific antibody targeting CD52 and CD20 for the treatment of B-cell malignancies

Methods : a Companion to Methods in Enzymology
Junpeng QiChristoph Rader

Abstract

Bispecific antibodies (biAb) targeting two different antigens or two distinct epitopes on the same antigen have demonstrated broad therapeutic utility. CD52 and CD20 are co-expressed on the cell surface of malignant B cells in B-cell non-Hodgkin lymphoma (B-NHL) and chronic lymphocytic leukemia (CLL) and increased expression of both antigens is detected on dividing or recently divided cells ("proliferative fraction") in CLL. The CD52-targeting monoclonal antibody (mAb) alemtuzumab (atz) not only depletes malignant B cells but also healthy CD52+ B and T lymphocytes and monocytes, causing severe immunosuppression. Loss of CD20 can occur in CLL after treatment with rituximab (rtx) and other CD20-targeting mAbs. To broaden the benefit of atz and rtx, we engineered an IgG1-like biAb, atz × rtx scFv-Fc. The Fc fragment of the biAb facilitates purification by Protein A affinity chromatography and supports a longer circulatory half-life. While atz × rtx scFv-Fc retained both antigen binding specificities, it showed superior binding to CD52+CD20+ B cells compared to CD52+CD20- T cells. Moreover, atz × rtx scFv-Fc mediated potent complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) in vitro and exhi...Continue Reading

Citations

Dec 15, 2020·Frontiers in Immunology·Valentina GriggioMarta Coscia
May 28, 2021·Frontiers in Oncology·Pablo OppezzoNicholas Chiorazzi
Jul 16, 2021·Leukemia & Lymphoma·Adrian Minson, Michael Dickinson
Sep 29, 2020·Recent Patents on Anti-cancer Drug Discovery·Romeo G Mihăilă
Dec 22, 2021·Integrative Biology : Quantitative Biosciences From Nano to Macro·Zhixin Cyrillus TanAaron S Meyer

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