Abstract 919: Comparative oncology approach to therapeutic monoclonal antibody development

Abstract

Introduction: Comparative oncology investigates the similarities in spontaneous carcinogenesis between humans and animals, to identify treatments that can benefit these patients. Companion animals (CA), like canines and felines, are of special interest when it comes to studying human cancers due to their exposure to the same environmental factors and develop tumors with similar features. The purpose of this study is to identify monoclonal antibodies (mAbs) that cross-reacts between humans and CA, and to characterize them in terms of specificity, functionality and efficacy, with an end goal of treating both species. Material and Methods: A panel of CA mAbs generated against a feline mammary carcinoma cell line was screened on multiple human cancer cell lines through flow cytometry to identify for positive binders. Shortlisted candidates were then characterized by biochemical and functional assays, specifically with antibody-drug conjugate (ADC) and western blot assays, as well as glycan studies. Ultimately, KP52, an IgG2 mouse monoclonal was selected. The antigen target was determined through immunoprecipitation coupled with mass spectrometry (IP-MS) and validated with cross-immunoprecipitation and siRNA knockdown. The specificity of KP52 on tissues was determined by immunohistochemistry. Results: Candidate mAb KP52 was generated from whole-cell immunization. KP52 showed strong positive binding to human cancer cells, such as breast cancer and ovarian cancer. Furthermore, KP52 demonstrated efficacy as an ADC with Saporin as the payload. Western blot results revealed the molecular weight of the antigen targets to be approximately 45kD to 50kD under reduced conditions. Glycan studies suggest that the epitope is glycan in nature, specifically an O-linked glycan. The antigen target was identified and validated. Histologically, KP52 does not stain normal tissues but binds to different malignant tissues, specifically stomach cancer, esophageal cancer, squamous cell carcinoma of the skin, ovarian cancer, breast cancer and lung cancer. Conclusion: KP52 antibody has the potential to be developed as an ADC against feline mammary cancer and various human cancers. Citation Format: Abigail Tan, James Hui, Eng Hin Lee, Andre Choo. Comparative oncology approach to therapeutic monoclonal antibody development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 919.