Safety immunopharmacology: Evaluation of the adverse potential of pharmaceuticals on the immune system

Abstract

The ICH S6R1 and S8 guidelines define a general framework for the immunotoxicity evaluation of biotechnology-derived pharmaceuticals and human pharmaceuticals, respectively. As severe and unpredicted adverse events dramatically showed in the recent years that the immune system is a critical aspect of drug safety, this framework needs to be revisited to enhance the prediction of nonclinical immune safety evaluation. Safety immunopharmacology is deemed to contribute to this awaited improvement by enabling early screening of the potential for drug candidates to induce unexpected immunosuppressive and immunostimulatory effects as well as nonimmune-mediated hypersensitivity reactions. Dedicated safety immunopharmacology can also generate mechanistic data to determine which relevant additional immunotoxicity studies should be conducted. Immunological assays and models that can be considered for use in the context of safety pharmacology studies are presented as well as perspectives for their timely development.

Optimization of the THP-1 activation assay to detect pharmaceuticals with potential to cause immune mediated drug reactions

“…HDRs are unavoidable and linked 66 to the intrinsic proprieties of the drug molecule and the genetic 67 predisposition of the patient (Adkinson et al, 2002). As severe 68 and unpredicted adverse events dramatically showed in the recent 69 years that the immune system is a critical aspect of drug safety, 70 enhanced prediction of nonclinical immune safety evaluation is 71 crucial (Descotes, 2012). 72 The process of developing a new chemical entity (NCE) into a 73 marketed pharmaceutical has many routes to failure and is very 74 expensive.…”

Immunological Responses of Arsenicum album 30CH to Combat COVID-19: Protocol for a Double-Blind, Randomized, Placebo-Controlled Clinical Trial in the Pathanamthitta District of Kerala

“…The timely, detailed investigation of the immunopharmacology of drug candidates is challenging [ 47 , 48 ]. In searching for therapeutic strategies against the COVID-19 pandemic, these essential investigations may be limited to a preliminary analysis or primary data obtained due to the pressing priority.…”

Immunosuppressive and Anti-Inflammatory Properties of Engineered Nanomaterials

“…Such structure activity relationships have been described for a variety of components of the immune system in the context of adverse immunostimulation, including, but not limited to, complement activation, platelet activation and induction of leukocyte procoagulant activity (Dobrovolskaia et al, 2012;Ilinskaya et al, 2013). However, studies investigating immunosuppressive properties of nanoparticles per se are scarce (Chen et al, 2004;Mitchell et al, 2009;Yamashita et al, 2009;Shen et al, 2011;2012). In part, this may be explained by methodological challenges and the lack of a systematic approach.…”

“…There is a growing body of evidence suggesting that immunotoxicity, defined as deregulated function of the immune system, contributes to the onset and development of various disorders including cancer and autoimmune diseases (Merk et al, 2001;Descotes, 2004;2012;Dobrovolskaia and Kozlov, 2005;Dietert, 2011). Nevertheless, it was not until recently that this relatively new field of toxicology became an important interface of novel drug design and pharmacology.…”