Work package 1

Project Title: Rapid detection of immunogenicity and adverse reactions to new compounds by in vitro assaying (WP1)


Host: Alcyomics Ltd, UK

Objectives: Predict sensitivity and potency of novel compounds using an in vitro human skin explant assay and correlate results with toxicity and modelling assessments from project 1.B. ESR will use ALC’s novel Skimune™ assay methodology, based on the use of culturing autologous dendritic cells, with the compound of interest and incubating with autologous T cells which in turn are added to autologous skin.

Expected Results: ALC will test monoclonal antibodies with standard positive controls, e.g. anti T cell antibody, OKT3 and compounds from FUJI and SAN. The resulting data will be utilised by UNEW and DTU (ESRs 1 and 8). This novel methodology will form the basis of training week 1 and knowledge exchange during secondments.




Project Title: Early toxicity prediction using hybrid-based modelling (WP1)

ESR 1    

Host: Newcastle University, UK

Objectives: Develop a modelling approach enabling prediction of toxicity by correlating the properties of molecules with experimentally determined toxicity, immunogenicity and hypersensitivity or allergic reactions. The ESR will assess the intrinsic toxicology of bioactive pharmaceuticals using a panel of in vitro methods, including effects on cell viability and/or proliferation (assessed using mitochondrial dye reduction methods) and genotoxicity (using in vitro COMET assay) on cell types described in section 2.1. Subsequently a range of modelling approaches will be developed/used by UNEW for the most effective representation of the available (bio)chemical characteristics of the candidate molecules and the production systems (e.g. structural characteristics of the molecule, detailed information on the expression vector and production organism).These  modelling approaches will include multivariate data analysis techniques, linear and non-linear clustering methods and kernel-based techniques will then be applied to model development/verification.

Expected Results: Methodology for prediction of toxicity of compounds on the basis of their properties formulated and the modelling approaches incorporated into the final framework. Tested on a range of model compounds and then on the industrial case studies from FUJI and SAN.