Abstract 78: Highly efficient antibody drug conjugation with a novel photoactivation strategy

Abstract

Abstract Meditope SnAP (site-specific novel antibody platform) technology is a novel way to target molecules to antibodies in a site specific, non-destructive fashion. A “meditope” is a proprietary peptide that can bind a meditope-enabled antibody in a unique site and in such a way that antigen binding is not compromised. This specific peptide antibody interaction can be readily employed for site-specific covalent conjugation of cytotoxic payloads to any meditope-enabled antibody. To facilitate covalent conjugation, the meditope peptide has been rationally designed with a photoactivatable side chain and the generation of the antibody-drug conjugate (ADC) occurs in a highly efficient manner following the specific binding of the meditope to the enabled antibody. To test the hypothesis that photoactivation would be an efficacious and homogenous way to make an ADC, meditope-enabled ADCs were designed and tested in vitro and in vivo. Toxin conjugation was tested, as was efficiency of covalent interaction following short-term exposure of the antibody peptide conjugates to a nondestructive wavelength of 340 nM. Photoactivation proved to be a highly efficient and scalable way to make an ADC. Payload stability was confirmed in vivo with multiple toxins and in vivo potency of two unique ADCs were tested in an EGFR positive gastric cancer xenograft as well as a HER2 positive ovarian cancer xenograft. The meditope-enabled photogenerated anti-HER2 ADC was benchmarked against conventionally conjugated T-DM1 and showed equivalent efficacy, but with the site-directed conjugated meditope ADC using less toxin. Meditope-directed photoactivated-controlled conjugation can be readily extended to any meditope-enabled antibody, resulting in a novel way to develop ADCs. This methodology, with its high efficiency, speed and homogeneity has evident advantages for the development of antibody-drug conjugates. Citation Format: Elisabeth Gardiner, Karin Forster, Robert McKenzie. Highly efficient antibody drug conjugation with a novel photoactivation strategy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 78. doi:10.1158/1538-7445.AM2017-78