IMMUNE ONCOLOGY & MODELLING
PRECLINICAL DISEASE MODELLING
Immune modelling is the modelling of an experimental system to test the immune response that may be associated with an infection, a metabolite or a drug. In immuno oncology it would be the key source to understanding the effective pathway of a therapeutic for example an oncolytic agent.
This is most appropriate when you are looking for a customised solution to a problem that cannot be solved by a single or standard assays.
Design experimental models for immune response
Preclinical assessment of drug efficacy or safety
Laboratory experiments in vitro (human) or in vivo
Why is immune modelling important?
You will need an immune model if developing an immunotherapeutic that is expected to function through generating an immune response (e.g. against tumours) or if the drug targets an immune condition (e.g. autoimmunity) or if the drug might generate an adverse immune response. This can also be combined with a mathematical model.
The adaptive immune system is a very complex system that is structured through a cascade of cells, receptors and cytokines that process, respond, initiate, memorise and deliver an immune response or tolerance. Understanding the threshold of ‘TOLERANCE’ is important to determine the mechanism of a therapeutic that exerts its effect through an immune response or that is likely to cross paths with the immune system.
In a sterile inflammatory state, as in a drug-induced effect, the immune effectors interact with the tissue of the body and/or the therapeutic agent to produce a cell mediated and/or antibody mediated immunity.
We have the relevant experience and insight to help you study the IMMUNE RESPONSE through the appropriate immune model and disease model.
How will you benefit from Immune Modelling?
Immune modelling will help you to test the efficacy and safety of a drug. You will understand:
- What is the immunologic mechanism of the disease and why is it important?
- Can the therapeutic generate an efficient immune response?
- What is the potential immune response to the therapeutic, and is it important?
- Working in immuno oncology, e.g. generating an immune response against an oncolytic virus or other form of tumour targeted antigen carrier
- Working in vaccine development against an infection or autoimmune disease
- Working in autoimmune disease
- Developing a large molecule therapeutic that requires more understanding of associated protein signaling pathways
- Developing a therapeutic (small or large molecule) that could interact with a non-target tissue.
How do we work with you?
We will first learn from you the mode of action of the therapeutic and the target tissue. From our team of protein and immunology experts, we will then design an experimental model for in vivo and/or in vitro (human) to test the immune response in the relevant disease model. The laboratory experiments will be carried out through an array of assays within our capacity.
Every study is tailored to the need of the therapeutic in reference, hence maybe different in timeline, process and pricing.
A Case Study
To study the role of heat shock proteins in immune mediated cell death and autoimmunity a model of diabetes was designed that consisted of transgenic expression of the target protein. Cell death of islet beta cells was initiated in a controlled dose dependent manner. The study successfully revealed that the (i) the initial beta cell death was responsible for the initiation of an immune mediated diabetes, and (ii) the immune response was increased by the over expression of heat shock protein. This study was important to understand the role of heat shock proteins in immunogenicity following tissue damage.
Dose dependent controlled death of islet beta cells was induced to initiate peptide targetted autoimmune response. The role of Heat shock protein in immune mediated cell death was studied. The overexpression of Heat shock protein (panel B) caused increased cell death as evidenced by reduction in insulin production on day 21 (diabetes development).
This also correlated with diabetes measurement (A = control, B = overexpression of Heat shock protein)
The death of beta cells and development of diabetes due to heat shock protein expression association was an immune mediated process.
Immunhistochemistry showed increased infiltrations (panel B) of MHC ClassII positive cells in the pancreas and inflammatory cytokines such as IL-1beta were elevated in serum.