Abstract 6348: ABN202 (αEGFR-interferon-β mutein), a potent antibody-cytokine fusion protein for the treatment of EGFR-positive non-small cell lung cancer

Abstract

Abstract ABN202 is an antibody-cytokine fusion protein consisting of interferon-β mutein (ABN102) molecularly fused to a anti-EGFR monoclonal antibody that recognizes the EGFR expressed on various types of cancer cells. In previous studies, we developed ABN102, a bio-better version of recombinant human interferon-β with hyperglycosylation via site-directed mutagenesis to improve stability, productivity, and pharmacokinetics properties. An addition of glycosylation at the N25 residue of ABN102 is expected to reduce the peripheral toxicity of ABN202, as it can shield the IFNAR2 binding interface. In this study, the binding ability and biological activity of ABN202 was evaluated in vitro models. ABN202 downregulates the EGFR protein expression and reduces EGFR phosphorylation by degrading target proteins via internalization in the EGFR-positive NSCLC cell line. In addition, we also determined the direct and indirect anti-cancer activity of ABN202 in preclinical models. Taken together, we suggest that ABN202 has potent anti-cancer activities, via direct cytotoxicity in EGFR-positive tumors and indirectly activating immune cells through Type I IFN signaling. we conclude ABN202 is a promising drug candidate for patients with EGFR-positive NSCLC. Citation Format: Heegeon Park, Saehyung Lee, Hayeon Park, Sunghyun Hong, Jaemun Kim, Sungyoul Hong, Ji-hyun Park, Young Kee Shin, Jun Young Choi, Na Young Kim. ABN202 (αEGFR-interferon-β mutein), a potent antibody-cytokine fusion protein for the treatment of EGFR-positive non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6348.