Abstract 4084: Potent anti-tumor activity of ABN202 (anti-EGFR antibody-interferon-beta mutein) through direct cytotoxicity and indirect immune activation against non-small cell lung cancer, regardless of EGFR mutation status

Abstract Epidermal growth factor receptor (EGFR) is overexpressed or mutated in many patients with non-small cell lung cancer (NSCLC). Targeting EGFR mutation by tyrosine kinase inhibitors (TKIs) has significantly improved overall survival (OS) in patients with EGFR mutations. However, many patients experience tumor recurrence due to various resistance mechanisms. Therefore, there is an unmet medical need for new treatment strategies for patients with EGFR-positive NSCLC, regardless of EGFR mutation status. ABN202 is an antibody-cytokine fusion protein (ACFP) that serves as a platform technology compromising the IFN-β mutein (ABN102) fused to various antibodies for specific tumor targeting. In a previous study, we designed ABN202 (αEGFR) to comprise an EGFR targeting antibody (Cetuximab) and IFN-β mutein (ABN102) and we confirmed anti-cancer activities of ABN202 against EGFR-positive NSCLC. In this study, the direct cytotoxicity of ABN202 (αEGFR) was evaluated in human NSCLC cell lines with various driving mutations and EGFR expression levels. The indirect immune activation was tested in human peripheral blood mononuclear cells (PBMCs) and human IFNAR1/2 knock-in (KI) mice. The in vivo efficacy was evaluated in human NSCLC xenograft mouse models and human IFNAR1/2 KI mouse models. ABN202 (αEGFR) demonstrates potent anti-tumor activity through direct cytotoxicity and indirect immune activation in NSCLC, regardless of EGFR mutation status. Taken together, we suggest that ABN202 (αEGFR) is a promising drug candidate against NSCLC, regardless of EGFR mutation status. Citation Format: Hee Geon Park, Sung Hun Cho, Ha Yeon Park, Mi Gyoung Jo, Ji Hyun Park, Myeung Ryun Seo, Ji Hyun Kim, Sung Youl Hong, Kyoung Song, Chan Gyu Lee, Hae Min Jeong, Sae Hyung Lee, Na Young Kim, Jun Young Choi, Young Kee Shin. Potent anti-tumor activity of ABN202 (anti-EGFR antibody-interferon-beta mutein) through direct cytotoxicity and indirect immune activation against non-small cell lung cancer, regardless of EGFR mutation status abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 4084.