Abstract 2662: Site specific ADC generation using SMARTag technology with programmable payload placement

摘要: Proceedings: AACR Annual Meeting 2014; April 5-9, San Diego, CA Antibody-drug conjugates (ADCs) are an exciting, new therapeutic option for cancer treatment.  ADCs offer the promise of targeted drug delivery with increased efficacy and safety.  Currently approved ADCs heterogeneous mixtures resulting from nonselective ligation to either cysteine or lysine residues.  This heterogeneity complicates pharmacokinetics pharmacodynamics these drugs.  Redwood Bioscience, Inc. has developed SMARTagTM technology platform that enables precise, programmable, site-selective chemical protein modification stable bioconjugate generation. Leveraging target sequence Formylglycine Generating Enzyme (FGE), proteins chemoenzymatically modified generate a precisely placed aldehyde functionality can be chemically elaborated.   Subsequently, novel chemistry is employed exploits this “aldehyde tag” site.  reaction, hydrazino-iso-Pictet-Spengler (HIPS) ligation, possesses two distinct advantages over current carbonyl ligations. First, HIPS proceeds quickly at near neutral pH in absence catalysts, allowing one-step labeling aldehyde-functionalized under mild conditions. Second, products very human plasma relative oxime-linked conjugates. Thus, exhibits combination stability speed unmatched by bioconjugation chemistries.  We will present our its application generating ADCs, including conjugation chemistries linker libraries.  These technologies have been applied generation panel site-specifically bioconjugates. Data preclinical tumor models PK studies highlighting safety how results impacted payload placement antibody presented. Citation Format: David Rabuka. Site specific ADC using SMARTag programmable placement. [abstract]. In: Proceedings 105th American Association Cancer Research; 2014 Apr 5-9; CA. Philadelphia (PA): AACR; Res 2014;74(19 Suppl):Abstract nr 2662. doi:10.1158/1538-7445.AM2014-2662