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Biomedicines 2017, 5(2), 28; doi:10.3390/biomedicines5020028

Addressing the Immunogenicity of the Cargo and of the Targeting Antibodies with a Focus on Deimmunized Bacterial Toxins and on Antibody-Targeted Human Effector Proteins

Department of Molecular Microbiology and Biotechnology, The George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv 69978, Israel
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Author to whom correspondence should be addressed.
Academic Editor: Stefan Barth
Received: 14 April 2017 / Revised: 23 May 2017 / Accepted: 31 May 2017 / Published: 2 June 2017
(This article belongs to the Special Issue Targeted Human Cytolytic Fusion Proteins)
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Abstract

Third-generation immunotoxins are composed of a human, or humanized, targeting moiety, usually a monoclonal antibody or an antibody fragment, and a non-human effector molecule. Due to the non-human origin of the cytotoxic domain, these molecules stimulate potent anti-drug immune responses, which limit treatment options. Efforts are made to deimmunize such immunotoxins or to combine treatment with immunosuppression. An alternative approach is using the so-called “human cytotoxic fusion proteins”, in which antibodies are used to target human effector proteins. Here, we present three relevant approaches for reducing the immunogenicity of antibody-targeted protein therapeutics: (1) reducing the immunogenicity of the bacterial toxin, (2) fusing human cytokines to antibodies to generate immunocytokines and (3) addressing the immunogenicity of the targeting antibodies. View Full-Text
Keywords: deimmunization; immunotoxins; immunocytokines deimmunization; immunotoxins; immunocytokines
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Grinberg, Y.; Benhar, I. Addressing the Immunogenicity of the Cargo and of the Targeting Antibodies with a Focus on Deimmunized Bacterial Toxins and on Antibody-Targeted Human Effector Proteins. Biomedicines 2017, 5, 28.

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