Studies on the immunogenicity of therapeutic proteins: methodological aspects of identifying and studying of the anti-drug antibodies
AbstractBiotechnological medicines (such as therapeutical proteins) are widely used in medical practice due to their high specificity to factors associated with the pathogenesis of diseases of various origins. However, the development of immune response to therapeutical proteins is big issue because it affects pharmacokinetic and pharmacodynamic profile, safety and efficacy of the drug. The clinical significance of therapeutic proteins immunogenicity mainly depends on its’ mechanisms of development and robustness, as well as specificity and affinity of the anti-drug antibodies (ADA). Identification, quantification and determination of anti-drug antibodies functional activity is the most important objective in drug development process as a key drug safety characteristic. This paper reviews different approaches of the therapeutic proteins immunogenicity assessment, choice of analytical methods for analysis and characterization of ADA during the clinical development process.
Keywords:immunogenicity; anti-drug antibodies; therapeutic proteins; monoclonal antibodies; screening and confirmatory studies; selection and validation of immunological methods; pharmacokinetics, efficacy; safety
For citation: Avdeeva Zh.I., Soldatov A.A., Alpatova N.A., Bondarev V.P., Mosyagin V.D., Korovkin A.S., Merkulov V.A. Studies on the immunogenicity of therapeutic proteins: methodological aspects of identifying and studying of the anti-drug antibodies. Immunologiya. 2024; 45 (1): 91–106. DOI: https://doi.org/10.33029/1816-2134-2024-45-1-91-106 (in Russian)
Funding. The study reported in this publication was carried out as part of publicly funded research project No. 056-00052-23-00 and was supported by the Scientific Centre for Expert Evaluation of Medicinal Products (R&D public accounting 121022000147-4). Open publication of the research results is allowed.
Conflict of interests. The authors declare no conflict of interests.
Authors contribution. The concept and design of the study – Avdeeva Zh.I., Bondarev V.P.; Collection and processing of material – Soldatov A.A., Alpatova N.A., Mosyagin V.D.; Writing the text – Avdeeva Zh.I., Alpatova N.A.; Editing – Korovkin A.S., Merkulov V.A.
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