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New Approaches to Prediction of Immune Responses to Therapeutic Proteins during Preclinical Development

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Abstract

Clinical studies show that immunogenicity observed against therapeutic proteins can limit efficacy and reduce the safety of the treatment. It is therefore beneficial to be able to predict the immunogenicity of therapeutic proteins before they enter the clinic. Studies using deimmunized proteins have highlighted the importance of T-cell epitopes in the generation of undesirable immunogenicity. In silico, in vitro, ex vivo and in vivo methods have therefore been developed that focus on identification of CD4+ T-cell epitopes in the sequence of therapeutic proteins. A case study of existing therapeutic proteins is presented to review these different approaches in order to assess their utility in predicting immunogenic potential.

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  1. The use of trade names is for product identification purposes only and does not imply endorsement.

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Acknowledgements

The authors are employed by Antitope Ltd, a company that specializes in immunogenicity testing and protein engineering. The authors would like to thank Dr Frank Carr for proof-reading the manuscript.

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Correspondence to Laura C. A. Perry.

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Perry, L.C.A., Jones, T.D. & Baker, M.P. New Approaches to Prediction of Immune Responses to Therapeutic Proteins during Preclinical Development. Drugs in R D 9, 385–396 (2008). https://doi.org/10.2165/0126839-200809060-00004

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