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Sagacity in antibody humanization for therapeutics, diagnostics and research purposes: considerations of antibody elements and their roles

Sagacity in antibody humanization for therapeutics, diagnostics and research purposes:... The humanization of antibodies for therapeutics is a critical process that can determine the success of antibody drug development. However, the science underpinning this process remains elusive with different laboratories having very different methods. Well-funded laboratories can afford automated high-throughput screening methods to derive their best binder utilizing a very expensive initial set of equipment affordable only to a few. Often within these high-throughput processes, only standard key parameters, such as production, binding and aggregation are analyzed. Given the lack of suitable animal models, it is only at clinical trials that immunogenicity and allergy adverse effects are detected through anti-human antibodies as per FDA guidelines. While some occurrences that slip through can be mitigated by additional desensitization protocols, such adverse reactions to grafted humanized antibodies can be prevented at the humanization step. Considerations such as better antibody localization, avoidance of unspecific interactions to superantigens and the tailoring of antibody dependent triggering of immune responses, the antibody persistence on cells, can all be preemptively considered through a holistic sagacious approach, allowing for better outcomes in therapy and for research and diagnostic purposes. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Antibody Therapeutics Oxford University Press

Sagacity in antibody humanization for therapeutics, diagnostics and research purposes: considerations of antibody elements and their roles

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Publisher
Oxford University Press
Copyright
© The Author(s) 2020. Published by Oxford University Press on behalf of Antibody Therapeutics.
eISSN
2516-4236
DOI
10.1093/abt/tbaa005
Publisher site
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Abstract

The humanization of antibodies for therapeutics is a critical process that can determine the success of antibody drug development. However, the science underpinning this process remains elusive with different laboratories having very different methods. Well-funded laboratories can afford automated high-throughput screening methods to derive their best binder utilizing a very expensive initial set of equipment affordable only to a few. Often within these high-throughput processes, only standard key parameters, such as production, binding and aggregation are analyzed. Given the lack of suitable animal models, it is only at clinical trials that immunogenicity and allergy adverse effects are detected through anti-human antibodies as per FDA guidelines. While some occurrences that slip through can be mitigated by additional desensitization protocols, such adverse reactions to grafted humanized antibodies can be prevented at the humanization step. Considerations such as better antibody localization, avoidance of unspecific interactions to superantigens and the tailoring of antibody dependent triggering of immune responses, the antibody persistence on cells, can all be preemptively considered through a holistic sagacious approach, allowing for better outcomes in therapy and for research and diagnostic purposes.

Journal

Antibody Therapeutics – Oxford University Press

Published: Apr 18, 2020

Keywords: therapeutics antibodies; VH/VL families; constant isotype; super antigen binding; antibody humanization

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