Antibody-drug conjugates for cancer therapy
Antibody - drug conjugates (ADCs) are drugs designed to target specific anti-cancer treatment. ADCs are immunoconjugates comprised of a monoclonal antibody attached to cytotoxic drug via a chemical linker. ADCs utilize monoclonal antibodies (mAbs) to specifically bind tumor-associated target antigen...
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| Format: | Book |
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Polish Pharmaceutical Society,
2021-11-01T00:00:00Z.
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| Summary: | Antibody - drug conjugates (ADCs) are drugs designed to target specific anti-cancer treatment. ADCs are immunoconjugates comprised of a monoclonal antibody attached to cytotoxic drug via a chemical linker. ADCs utilize monoclonal antibodies (mAbs) to specifically bind tumor-associated target antigens and deliver a highly potent cytotoxic agent. ADCs were designed to enhance the therapeutic index and minimize the toxicity of anticancer agents and overcome multidrug resistance in target cells. Upon intravenous administration, ADCs bind to their target antigens and are internalized through receptor-mediated endocytosis. This facilitates the subsequent release of the cytotoxin, which eventually leads to apoptotic death of the cancer cell. The three components of ADCs (mAb, linker and cytotoxin) affect the efficacy and toxicity of the conjugate. mAB should ensure high tumor specificity, target affinity and low immunogenicity. Linkers are designed to be stable in the blood stream and labile at the cancer site to allow rapid release of cytotoxic drug. Cytotoxin should be soluble in aqueous environment of mAb, stable in the blood stream and in the acidic environment of lysosome, high potent at low concentrations, and its structure should allows for conjugation. The structure of ADC is dominated by the antibody backbone, and consequently, its properties determine majority of ADME processes. ADCs are characterized by poor oral bioavailability, long half-life, neonatal Fc receptor-dependent recycling, slow clearance, low volume of distribution, nonlinear pharmacokinetics and immunogenicity. Toxicity of ADCs in healthy tissue is mostly caused by cytotoxin. Uptake of ADCs into normal cells is mediated by target-dependent or target-independent mechanism. Currently, eleven ADCs were approved for clinical use by FDA, and more than ninety were still during clinical trials in June 2020. In this paper pharmacokinetic properties of ADCs were discussed in detail, and also their structure, anti-tumor activity and toxicity. |
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| Item Description: | 0014-8261 10.32383/farmpol/144250 |