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ANTISOMA: A Computational Pipeline for the Reduction of the Aggregation Propensity of Monoclonal Antibodies

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GeNeDis 2018

Abstract

Monoclonal antibodies (mAbs) constitute a promising class of therapeutics, since ca. 25% of all biotech drugs in development are mAbs. Even though their therapeutic value is now well established, human- and murine-derived mAbs do have deficiencies, such as short in vivo lifespan and low stability. However, the most difficult obstacle to overcome, toward the exploitation of mAbs for disease treatment, is the prevention of the formation of protein aggregates. ANTISOMA is a pipeline for the reduction of the aggregation tendency of mAbs through the decrease in their intrinsic aggregation propensity, based on an automated amino acid substitution approach. The method takes into consideration the special features of mAbs and aims at proposing specific point mutations that could lead to the redesign of those promising therapeutics, without affecting their epitope-binding ability. The method is available online at http://bioinformatics.biol.uoa.gr/ANTISOMA.

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Abbreviations

APRs:

Aggregation-prone regions

CDRs:

Complementarity determining regions

FDA:

US Food and Drug Administration

mAbs:

Monoclonal antibodies

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Acknowledgments

This work has been partly supported by the University of Piraeus Research Center.

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Correspondence to Vassiliki A. Iconomidou .

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Nastou, K.C. et al. (2020). ANTISOMA: A Computational Pipeline for the Reduction of the Aggregation Propensity of Monoclonal Antibodies. In: Vlamos, P. (eds) GeNeDis 2018. Advances in Experimental Medicine and Biology, vol 1194. Springer, Cham. https://doi.org/10.1007/978-3-030-32622-7_34

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