Predicting the Immune Response to a New Biologic
Peptide binding to MHC II and subsequent presentation to CD4 T cells are decisive events that occur upstream of any adaptive or cellular immune response to a foreign body, in this case, a biologic.
In deimmunisation projects, Immunitrack applies the unique in vitro screening platform called NeoScreen®. With this technology Immunitrack offers to detect potential immunogenic epitopes in biologics and subsequently identify amino acid substitutions that may reduce epitope binding to MHC II molecules and reduce immunogenicity risk by preventing the anti-drug antibody (ADA) response. Figure 1 illustrates a typical workflow to evaluate and reduce immunogenicity.
Figure 1. Deimmunisation workflow brief overview. 1. Partner or client approaches Immunitrack with pre-lead biological drug candidates. 2. Immunitrack makes immunogenicity assessments to evaluate the risk of a T cell response and ADA formation. 3. This information is then used to direct deimmunisation, where the biologic is re-engineered to reduce the risk of unwanted immune responses.
Early Derisking of Biotherapeutics Increases Safety and Efficacy
How do you know whether your biologic will provoke an unwanted immune response in patients? Part of the answer lies in how the immune system is likely to recognise epitopes from the biologic.
An ideal biologic should combine maximum efficacy with low or no propensity for recognition by the immune system. Reducing the immunogenicity of any biologic without compromising its function will improve its safety and efficacy profile and should increase the likelihood of a positive clinical outcome.
The processes that lead to the formation of ADAs and an unwanted immune response to a biologic are complex, but decisively linked to the binding of drug-derived peptides (epitopes) to Major Compatibility Complex Class II (MHC II) molecules (Figure 2).
Assessing and reducing the binding of potential epitopes from a new biologic to MHC II is a powerful strategy to reduce the likelihood of ADA development and prevent an ADA response.
Figure 2. Anti-drug antibody development. An individual is exposed to a new biologic. Antigen presenting cells form complexes of MHC II with epitopes from the biologic and present these complexes to CD4 T cells. CD 4 T cells become activated when they recognise immunogenic complexes, causing them to release cytokines that trigger an immune response which includes the formation of anti-drug antibodies (ADAs) by plasma B cells. Deimmunisation prevents ADA formation by identifying and removing CD4 T cell epitopes in candidate biologics.
World Leaders in Immunogenicity Prediction
Given the low precision of current MHC II prediction algorithms we do not recommend relying on in silico immunogenicity assessments. Immunitrack has world-leading expertise in assessing epitope binding to MHC I and MHC II molecules. Our NeoScreen® technology has helped clients and partners in both vaccine development and deimmunisation efforts.