Abstract PO-065: SIWA318H, an advanced glycation end product (AGE) targeting antibody, is efficacious in a humanized mouse xenograft model for pancreatic cancer

Abstract

Abstract SIWA318H is a novel monoclonal antibody that selectively targets a biomarker (an advanced glycation end product) found on the surface of cells exhibiting a combination of: (a) an abnormally high level of aerobic glycolysis, a process known to be associated with initiation and progression of cancer as well as metastasis; and (b) oxidative stress. Cells with this biomarker are often dysfunctional and associated with aging, cancer, and infectious diseases. In this study, we evaluated the antitumor activity of SIWA318H in a humanized xenograft model for pancreatic cancer. SIWA318H was found to react to pancreatic cancer cells (PSN1) and cancer associated fibroblasts (CAF08) using immunofluorescent staining. SIWA318H also showed strong reactivity with tumor xenografts derived from patients with pancreatic cancer as demonstrated by immunohistochemistry. Humanized CD34+ NSG mice were injected subcutaneously with PSN1 pancreatic cancer tumor cells. Ten days later, mice were randomized and enrolled in one of the following groups (n=16/group): 1) IgG1 isotype control (20mg/kg, BIWx1 followed by 10 mg/kg, BIWx2); 2) high dose SIWA318H (20mg/kg, BIWx1 followed by 10 mg/kg, BIWx2); and 3) low dose SIWA318H (10 mg/kg, BIWx1 followed by 5mg/kg, BIWx2). Tumors in mice treated with SIWA318H grew significantly slower than those in mice treated with isotype control antibody (p<0.001). After 3 weeks of treatment with the high dose or the low dose of SIWA318H, the tumor growth was suppressed by 68.8% and 61.5%, respectively, when compared to the isotype antibody control (ANOVA p<0.002). Moreover, a significant increase in complete remission (CR) rate was observed in mice receiving high (60%, p<0.05) or low dose (77.8%, p<0.02) of SIWA318H treatment compared with the control mice (6.7%). No significant antibody treatment related weight loss in mice was observed. These results provide compelling evidence that SIWA318H is a promising novel therapeutic for pancreatic cancer. Additional studies to better understand the mechanism of action of this novel immunotherapy agent are underway. Citation Format: Ashley Jensen, Gabriela R. Rossi, Ruben Muñoz, Kimberly Brothers, Lewis Gruber, Misty Gruber, Haiyong Han. SIWA318H, an advanced glycation end product (AGE) targeting antibody, is efficacious in a humanized mouse xenograft model for pancreatic cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-065.