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- W1604609317 abstract "Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CAAntibody-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 are heterogeneous mixtures resulting from nonselective ligation of drug to either cysteine or lysine residues. This heterogeneity complicates the pharmacokinetics and pharmacodynamics of these drugs. Redwood Bioscience, Inc. has developed the SMARTagTM technology platform that enables precise, programmable, site-selective chemical protein modification and stable bioconjugate generation. Leveraging the target sequence of Formylglycine Generating Enzyme (FGE), proteins are chemoenzymatically modified to generate a precisely placed aldehyde functionality that can be chemically elaborated. Subsequently, novel ligation chemistry is employed that exploits this “aldehyde tag” site. This new reaction, the hydrazino-iso-Pictet-Spengler (HIPS) ligation, possesses two distinct advantages over current carbonyl ligations. First, the HIPS ligation proceeds quickly at near neutral pH in the absence of catalysts, allowing for one-step labeling of aldehyde-functionalized proteins under mild conditions. Second, HIPS ligation products are very stable in human plasma relative to an oxime-linked conjugates. Thus, the HIPS ligation exhibits a combination of stability and speed at near neutral pH that is unmatched by current carbonyl bioconjugation chemistries. We will present our novel protein modification platform and its application to generating ADCs, including our new conjugation chemistries and linker libraries. These technologies have been applied to the generation of a panel of site-specifically modified bioconjugates. Data from preclinical tumor models and PK studies highlighting the efficacy and safety of these ADCs and how these results are impacted by payload placement to the antibody will be presented.Citation Format: David Rabuka. Site specific ADC generation using SMARTag technology with programmable payload placement. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2662. doi:10.1158/1538-7445.AM2014-2662" @default.
- W1604609317 created "2016-06-24" @default.
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- W1604609317 date "2014-09-30" @default.
- W1604609317 modified "2023-09-27" @default.
- W1604609317 title "Abstract 2662: Site specific ADC generation using SMARTag technology with programmable payload placement" @default.
- W1604609317 doi "https://doi.org/10.1158/1538-7445.am2014-2662" @default.
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