Abstract 2938: Avaren-Fc: a novel lectin-Fc fusion protein for treatment of ovarian cancer

Abstract Ovarian cancer (OVCA) is the deadliest gynecological malignancy and the fifth leading cause of cancer death in females in the United States. Despite advancements in the treatment options, current therapies lack specificity for tumor cells and fail to generate a robust anti-tumor immune response. In this study, we use a novel lectin-Fc fusion protein, named Avaren-Fc (AvFc), to target the abnormal, increased density of N-linked high-mannose-type glycans on the OVCA cell surface. Upon binding to clusters of these glycans on malignant cells, AvFc is postulated to induce antibody-dependent cell-mediated cytotoxicity (ADCC) by engaging Fc-bearing effector immune cells, such as natural killer cells. This study explores AvFc’s therapeutic potential against OVCA utilizing in vitro experiments and in vivo evaluations using the syngeneic ID8 OVCA mouse model. AvFc’s effects were evaluated utilizing flow cytometry and an in vitro luciferase-based ADCC reporter assay using a FcγRIIIa-expressing cell line, where AvFc exhibited dose-dependent binding and demonstrated a variable, yet significant degree of ADCC to four human (A2780, CAOV3, SKOV3, and SW626) and two murine (ID8 and ID8-VEGF-Def2b) OVCA cell lines. The antitumor effects of AvFc were evaluated in the ID8 OVCA model, where mice were intraperitoneally (i.p.) challenged with 2 million ID8 cells and 7 days later AvFc treatment was administered at 25 mg/kg i.p. every other day, for a total of 15 doses. The survival analysis revealed that, as of 28 days post-treatment, 75% of AvFc-treated animals remain alive, in contrast to 40% in the mutant AvFc control group and 0% in the vehicle control group. To assess the impact of this 15-dose regimen of AvFc on the tumor immune microenvironment in the ID8 OVCA model, immune cell profiling was performed at 36 days post-tumor challenge using cytometry by time-of-flight (CyTOF) on both the peritoneal fluid and spleen. CyTOF analysis revealed that AvFc treatment significantly increased total leukocytes (p<0.05; one way ANOVA with Tukey’s multiple comparisons) including TCRγδ+, TCRβ+, and TCRβ+CD4+ T cells in the spleen compared to all other treatment groups. Additionally, AvFc treatment significantly increased CD8+ T cells expressing the degranulation marker CD107a in the peritoneal fluid (p<0.05) relative to vehicle and healthy controls, suggesting that AvFc treatment induced a significant adaptive immune response against the murine ID8 OVCA challenge. These findings highlight AvFc’s promising efficacy and immunostimulatory activity, supporting its potential as a novel targeted immunotherapeutic candidate for the treatment of OVCA. Citation Format: Katarina Mayer, Noel Verjan-Garcia, Nobuyuki Matoba. Avaren-Fc: a novel lectin-Fc fusion protein for treatment of ovarian cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2938.