Sie befinden Sich nicht im Netzwerk der Universität Paderborn. Der Zugriff auf elektronische Ressourcen ist gegebenenfalls nur via VPN oder Shibboleth (DFN-AAI) möglich. mehr Informationen...
Antibody drug conjugates (ADCs) are a therapeutic class offering promise for cancer therapy. The attachment of cytotoxic drugs to antibodies can result in an effective therapy with better safety potential than nontargeted cytotoxics. To understand the role of conjugation site, we developed an enzymatic method for site-specific antibody drug conjugation using microbial transglutaminase. This allowed us to attach diverse compounds at multiple positions and investigate how the site influences stability, toxicity, and efficacy. We show that the conjugation site has significant impact on ADC stability and pharmacokinetics in a species-dependent manner. These differences can be directly attributed to the position of the linkage rather than the chemical instability, as was observed with a maleimide linkage. With this method, it is possible to produce homogeneous ADCs and tune their properties to maximize the therapeutic window.
[Display omitted]
► Site-specific conjugation of diverse payloads can be achieved with transglutaminase ► Efficient conjugation was achieved at multiple positions throughout an antibody ► Site of conjugation has significant impact on ADC stability and pharmacokinetics ► Differences in ADC stability and pharmacokinetics are species dependent
Antibody drug conjugates (ADCs) can deliver drugs attached to antibodies to selectively targeted cells. Strop et al. develop an enzymatic method for site-specific antibody-drug conjugation to examine the role of the conjugation site and find that the conjugation site has an impact on ADC stability and pharmacokinetics.