Endocytosis and Internalization Potency Detection

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  • Published date: October 30, 2019
    • Shirley, New York, United States

One important mechanism of action of therapeutic antibodies is to induce internalization and turnover of cell surface receptors, resulting in receptor down-modulation as well as antibody endocytosis. This receptor-mediated internalization exhibits great potential for various therapeutic or diagnostic applications. Particularly, due to their abilities of specific binding and intracellular transfer, internalizing antibodies make an excellent vehicle for targeted delivery of drugs, toxins, enzymes or DNA into the cytosol of indicated cells. Therefore, one of the prerequisites for antibodies designed for antibody drug conjugate (ADC) is to induce rapid receptor internalization, so as to ensure cell-specific drug delivery. After internalization, antibody-receptor complexes can either recycle back to the plasma membrane or be degraded by late endosomes and lysosomes. Of note, when at low doses, receptor-mediated internalization activities usually outcompete Fc-mediated recycling, which is based on Fc-FcRn binding and can prevent antibodies from degradation. This can probably explain why internalizing antibodies commonly display shorter half-lives in contrast to antibodies against soluble antigens. https://www.creative-biolabs.com/drug-discovery/therapeutics/endocytosis-and-internalization-potency-detection.htm

Jerry Carter
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