Immunotoxicology

Cyprotex and parent company Evotec have combined expertise in immunotoxicity which spans from early discovery through to the clinic.

We have a full picture of the entire drug discovery and development continuum and can support you at every stage of your project. The scientific expertise and capabilities can be accessed as fee-for-services or as part of partially or fully integrated programs.

The generation of adverse immunological reactions towards a therapeutic agents can have severe implications in terms of drug safety and efficacy following administration in a clinical setting. Classical in vivo models often fail to fully recapitulate the complexity of the human immune response and experimental outcomes may not adequately reflect the safety of candidates entering the pipeline.

As part of an early de-risking strategy, we have developed a battery of in vitro  assays to assess both the immunogenic and cytotoxic potential of myriad drug modalities including biologics, oligonucleotides and small molecules. Our on-site biobank houses a plethora of HLA-typed immunocompetent cells isolated from the blood of healthy, human donors. This allows the option to evaluate both inter-individual and population wide responses to test articles if desired. All assays are developed using our high-throughput screening platform for maximum efficiency; however, low throughput options are also available for those wishing to test a smaller number of compounds.

We offer assays using peripheral blood mononuclear cells (PBMC), CD14 positive monocytes, dendritic cells (DC), naïve T-cells, memory T-cells and neutrophils. The assays to investigate potential immunotoxicity of drugs in development include:

• The PBMC cytotoxicity assay utilizes cells isolated from multiple individuals which are cryopreserved in our biobank. The assay provides a high throughput assessment of the cytotoxicity of candidate compounds in vitro and measures drug-induced cellular ATP depletion and LDH release. It can also provide an initial insight into how immune cells from different donors respond to candidate drugs in development.
• PBMC proliferation assay. This assay investigates the immunogenicity of test articles based upon their potential to stimulate PBMC proliferation. Inter-individual variability in immunogenicity can also be examined by assessing PBMC isolated from multiple donors (>6 donors available for multi-donor studies). Supernatants from test article-treated cells are also profiled to determine the nature of the drug-induced cytokine profile.
  
• PBMC cytokine release assay. This assay assesses the ability of test articles to activate both T & B cells by measuring the release of relevant cytokines. It can be used to determine the propensity of test articles to cause deleterious acute events i.e., cytokine storm syndrome or latent unwanted immunogenicity. It can be readily combined with our PBMC proliferation assay to provide a greater level of insight into the immunogenic affects elicited by candidate drugs. Contact us to learn more.
• Dendritic cell activation assay; dendritic cells (DC) are innate immune cells that provide a critical link to the adaptive immune system. DC are antigen presenting cells responsible for the recognition, capture, processing and presentation of antigens to T-cells. This assay assesses the ability of test articles to stimulate the innate immune activation by measuring key biomarkers such as pro-inflammatory cytokine release in conjunction with cell viability. This approach is particularly useful with regards to determining the efficacy and safety of vaccine formulations/adjuvants.