Sepsis target validation for repurposing and combining complement and immune checkpoint inhibition therapeutics

Rodrigues, Patrícia R.S. ORCID: https://orcid.org/0000-0003-0768-0013, Picco, Noemi, Morgan, B. Paul ORCID: https://orcid.org/0000-0003-4075-7676 and Ghazal, Peter ORCID: https://orcid.org/0000-0003-0035-2228 2021. Sepsis target validation for repurposing and combining complement and immune checkpoint inhibition therapeutics. Expert Opinion on Drug Discovery 16 (5) , pp. 537-551. 10.1080/17460441.2021.1851186

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Abstract

Introduction: Sepsis is a disease that occurs due to an adverse immune response to infection by bacteria, viruses and fungi and is the leading pathway to death by infection. The hallmarks for maladapted immune reactions in severe sepsis, which contribute to multiple organ failure and death, are bookended by the exacerbated activation of the complement system to protracted T-cell dysfunction states orchestrated by immune checkpoint control. Despite major advances in our understanding of the condition, there remains to be either a definitive test or an effective therapeutic intervention. Areas covered: The authors consider a combinational drug therapy approach using new biologics, and mathematical modeling for predicting patient responses, in targeting innate and adaptive immune mediators underlying sepsis. Special consideration is given for emerging complement and immune checkpoint inhibitors that may be repurposed for sepsis treatment. Expert opinion: In order to overcome the challenges inherent to finding new therapies for the complex dysregulated host response to infection that drives sepsis, it is necessary to move away from monotherapy and promote precision for personalized combinatory therapies. Notably, combinatory therapy should be guided by predictive systems models of the immune-metabolic characteristics of an individual’s disease progression.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Additional Information:	This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/)
Publisher:	Informa Healthcare
ISSN:	1746-0441
Date of First Compliant Deposit:	6 January 2021
Date of Acceptance:	11 November 2020
Last Modified:	07 May 2023 19:27
URI:	https://orca.cardiff.ac.uk/id/eprint/137356

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