Tools to Predict Clinical Immunogenicity

Background:

Immunogenicity, the propensity of a product to elicit an immune response to itself or related structures, may be desirable (e.g. vaccine candidates) or undesirable (e.g. therapeutic proteins).  For the latter, immunogenicity has the potential to reduce or eliminate the therapeutic benefit it is intended to provide and may even lead to adverse clinical events.  Because of its potential impact on safety and efficacy of therapeutic protein products, evaluation of a product’s immunogenicity is required by regulatory authorities (e.g. FDA and EMA).  However, the predictive value of animal studies is low, and because immunogenicity can be based on product-, treatment- and patient-specific factors, evaluation of a product’s immunogenicity risk can be challenging to accurately assess prior to human clinical trials. In some cases, a product’s immunogenicity may not be fully known until after it has been approved and used in larger patient populations over extended periods of time. There is an unmet need for a reliable tool that can be used to more accurately predict both the likelihood and level of clinical immunogenicity prior to administration in human subjects.

Technology Overview:

This suite of tools, invented at the University at Buffalo, enables reliable measurement and prediction of an antigen’s immunogenic potential based on mechanism-based markers, namely to those specific to the subcutaneous route of administration.   One tool (030-7497) provides a stimulation index as well as an indication of immune cell migratory potential, both of which can be measured against a control and compared to those of approved therapeutic proteins.  To date, the tool has been demonstrated with multiple proteins, including adalimumab (Humira™), emicizumab (Hemlibra™) and the SARS-CoV-2 spike subunit 1 ‘S1’ protein, and the relative immunogenicity of each reflects that seen in the clinic. The second tool (030-7816) provides a microphysiological platform (i.e. skin-on-a-chip) that mimics the multistep immune activation cascade, more accurately reflecting the coordinated sequence of antigen uptake, processing, presentation, co-stimulation and effector amplification that ultimately drives antigen-specific antibody formation.

Advantages:

• Ability to predict clinical immunogenic response prior to administration in a human subject
• Provides mechanistic insights into the driver(s) of immunogenicity
• Can be generalized to a patient population or tailored to predict immunogenicity on a subject-by-subject basis

Applications:

• Biomedical Research
• Drug and Vaccine Development
• Personalized Medicine

Intellectual Property Summary:

Patent pending.

Stage of Development:

In vitro.

Licensing Status:

Available for licensing or collaboration.

Publication link(s):

• 030-7497: Communications Medicine volume 3, Article number: 174 (2023)
• 030-7816: unpublished