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Changes at "But Montaigne, who liked to fancy that his family (the Eyquem line) was of English extraction"
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Antibody-drug conjugates (ADCs) are on the brink of widespread use for the targeted treatment of cancer. ADCs manage the toxicity of drugs with unacceptable narrow therapeutic windows by guiding highly toxic compounds to the target cells, thereby sparing healthy cells. Drug-to-antibody ratio (DAR) is an important quality attribute of ADC drugs, which represents the average number of antibody-conjugated small molecule cytotoxic drugs. Lower DAR will reduce the potency of ADC, but higher DAR will affect the ADC analysis pharmacokinetics and toxicity. In addition, the conjugation method is an important factor affecting DAR. Only by selecting a suitable conjugation technology can the ADC toxin be conjugated to the antibody uniformly and stably.
\nWhy Does ADC Need DAR Analysis?
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Drug distribution can be differentiated because conjugation reaction at different amino acid residues of mAbs leads to different types of ADCs, such as lysine conjugation, cysteine conjugation, or engineered conjugation. Different drug distribution may contribute to very different pharmacokinetics and toxicological properties, directly affecting the efficacy and safety of ADCs. Therefore, drug distribution must be characterized to ensure the efficiency and safety of ADCs. The DAR calculation is closely relevant to the drug load distribution. Normally, analysis of the average DAR as well as its drug load distribution should consider several factors, including conjugation strategies, linkers, small-molecule payloads and platform applications.DAR and Drug Distribution Analysis Services
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Ultraviolet-Visible (UV/Vis) Spectroscopy
UV/Vis spectroscopy is a simple and convenient method to determine protein concentrations as well as the average number of drugs that are conjugated to the antibody in an ADC. This method requires that the UV/VIS spectra of the drug and antibody have different Amax values. The average DAR can be determined by using the measured ADC absorbance and the extinction coefficient of mAb at Amax and the extinction coefficient of drug at Amax. Currently, this technology has been widely used in the detection of various cytotoxic ADC drugs, such as maytansinoid DM1, methotrexate, CC-1065 analogues, adriamycin, the doxorubicin, calicheamicin analogues and vc-MMAE.
