ProImmune Ltd., a provider of services for immunogenicity risk assessment for biologics, has launched DC T Cell Proliferation Assays based on its class-leading CFSE detection platform to assess the immunogenicity of whole proteins. This highly sensitive and versatile assay measures if candidate proteins induce helper CD4+ T cell proliferation that may lead to anti-drug antibody responses or other unwanted immunogenicity.
The novel assay significantly improves data quality over traditional radioactive assay methods. It also offers the possibility for phenotyping T cell responses further, for example, to understand more clearly the actual observed phenomena during clinical stage development.
The assay, which is run on samples from ProImmune’s unique high resolution tissue-typed bank of healthy PBMC donor samples, arguably represents the most powerful tool yet for comparing the antigenicity of different candidate proteins at a preclinical stage.
In the assay, monocyte derived dendritic cells (DCs), obtained from healthy PBMC donors, are loaded with the candidate protein. These loaded and activated DCs process and present the candidate protein to CFSE-labeled PBMCs. Where the candidate protein has immunogenic properties, CD4+ T cell proliferation occurs. This is detected through a CFSE-based flow cytometric assay to accurately 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 applications of the assay are wide-ranging. It allows for an overall comparison of the T cell driven antigenicity of any number of drug candidates at a preclinical stage. Crucially 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, CEO 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 programs. Like other services from ProImmune this assay will save our customers time and money, and empower them with deeper knowledge that enables them to make more informed decisions at all stages of preclinical and clinical development.”