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Immunogenicity and PK/PD


Repetitive administration of protein-based therapeutics to immunocompetent patients can elicit immune responses in the form of Anti-Drug Antibodies (ADAs). One form of immune response is the activation of B cells, which produce antibodies that bind to the proteins and reduce or eliminate their therapeutic effects. The majority of ADA to therapeutic monoclonal antibodies (mAbs) are directed against the antigen-binding site of the therapeutic mAb, and hence are neutralizing. This nature of the ADA response explains why fully human antibodies can still be immunogenic. On the other hand, the complex formation of protein-ADA may culminate a depot effect which impedes the turnover of the protein. In such rare scenario, favorable therapeutic benefits may be expected. On a different subject, allometric scaling and correlation are compared between proteins and drugs.

All therapeutic proteins have antigenic potential and could elicit an immune response with the consequent production of anti-drug antibodies (ADA). The immunogenic response can be manifested in two ways: The neutralizing effect of ADA reduces or eliminates the therapeutic response or even develops undesirable adverse effects The complexation of ADA-protein impedes the turnover of the circulating protein and favors the therapeutic effect. Allometry or biological scaling is the change of scalable PK/PD attributes in relation to changes in body size. It is interesting to note that allometric scaling is more evident for proteins compared with small molecule drugs. This can be explained by “selfness” or “sameness” of protein perceived by the organisms as opposed to the vastly different small molecules.

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Pharmacotherapy: Understanding Biotechnology Products

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