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AcroBiosystems社 Frontiers in Therapeutic Antibodies: ADC, the Magic Bullets

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Frontiers in Therapeutic Antibodies: ADC, the Magic Bullets

 


 

fig1.jpgImproved Methodology for the Synthesis of a Cathepsin B Cleavable Dipeptide Linker, Widely Used in Antibody-Drug Conjugate Research

 

Cathepsin B as a key lysosomal protease in ADCs

 

Cathepsin B is a lysosomal protease that is involved in lysosomal disruption and apoptosis. Overexpression of cathepsin B is often accompanied by altered trafficking of the enzyme to the plasma membrane and secretion into the extracellular milieu and is a major participant in proteolysis in the human body. Lysosomal protease-sensitive linkers/peptide-based linkers are commonly used in ADC designs which are stable in the systemic circulation and release the drug specifically in the target cells. Examples include valine–citrulline (Val–Cit, found in Adcetris®). There are six approved ADCs cleaved by cathepsin B.

 

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fig2.jpg 

Semi-mechanistic Multiple-Analyte Pharmacokinetic Model for an Antibody-Drug-Conjugate in Cynomolgus Monkeys.

 

Anti-MMAE Antibodies: For PK/PD Studies on MMAE-ADC

 

As reported, the ADCETRIS® combination significantly improves overall survival in newly diagnosed patients with Advanced Hodgkin Lymphoma. ADCETRIS is an ADC with a monomethyl auristatin E (MMAE) payload. MMAE is a potent anti-cancer microtubule-targeting agent (MTA) used as a payload in five approved MMAE-containing ADCs and multiple ADCs in clinical development to treat different types of cancers. ACROBiosystems has developed anti-MMAE antibodies facilitating the PK and PD evaluation of ADCs. It also can be used in the qualitative detection of DAR value 

 

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