DC T cell proliferation assay assesses whole proteins
Sets new standards of analysis using CFSE technology
ProImmune, a UK provider of services for immunogenicity risk assessment for biological drugs, has introduced DC T cell proliferation assays based on its CFSE detection technology to assess the immunogenicity of whole proteins. This assay measures whether candidate proteins induce helper CD4+ T cell proliferation that may lead to anti-drug antibody responses or other unwanted immunogenicity.
The Oxford-based firm says the assay significantly improves data quality compared with traditional radioactive assay methods. It also offers the possibility for phenotyping T cell responses to help researchers understand more clearly the observed phenomena during clinical stage development.
The assay, which is run on samples from ProImmune’s high resolution tissue-typed bank of healthy PBMC donor samples, is a powerful tool for comparing the antigenicity of different candidate proteins at a preclinical stage, the firm added.
In the assay, monocyte derived dendritic cells (DCs) obtained from healthy PBMC donors are loaded with the candidate protein. These DCs process and present the candidate protein to CFSE-labelled PBMCs. Where the candidate protein has immunogenic properties, CD4+ T cell proliferation occurs. This is detected through a CFSE-based flow cytometric assay to determine the percentage of proliferating CD4+ T cells.
Antigen presentation by dendritic cells avoids assay interference due to direct modulation of target T cells by the candidate drug, and allows the relative antigenicity of different leads to be compared directly.
The assay allows for an overall comparison of the T cell driven antigenicity of any number of drug candidates at a preclinical stage. It can also be used for assessing the impact on antigenicity of factors other than protein sequence. Such differences may include a comparison of biosimilars, protein modifications, degradation products, chemical entities given in combination therapies, and other parameters related to manufacturing processes, excipients, drug formulation and stability.
Dr Nikolai Schwabe, chief executive of ProImmune, said: ‘Our new DC T cell assay delivers what our customers have come to expect from ProImmune – translation of the best science into ready-to-use tools that deliver a clear competitive advantage to their development programmes.’
