Abstract PO-058: Anti-cancer activity of NTAX-44 (bioprocessed arsenic trioxide) on pancreatic cancer cell line

Abstract

Abstract Purpose: Pancreatic Cancer remains to be highly lethal malignancy mainly because of a high incidence of drug resistance. Because of this, there is a great need for new therapies which can improve overall therapeutic outcomes in pancreatic cancer patients. Arsenic trioxide is an approved drug for the treatment of acute promyelocytic leukemia (APML) and is in the experimental stage for use in different malignancies. Earlier in-vitro studies on human pancreatic cell lines have shown that arsenic trioxide has potent anti-proliferative effects with induction of apoptosis. NTAX-44 is a novel orally administrable Arsenic trioxide that is derived using green chemistry based patented technology. This compound is bioavailable when administered orally, and it has demonstrated good safety and tolerability in bioavailability clinical trials. In the present study, we conducted preclinical studies to evaluate the anti-proliferative effect and inhibition of programmed cell death ligand-1 (PD-L1) expression activity by NTAX-44. Method: The effect of NTAX-44 was assessed on the viability of MIA-Pa-Ca-2 cell lines grown as monolayers by MTS assay. We further checked the expression of PD-L1 in MIA-Pa-Ca-2 cell line treated with NTAX-44 by flow cytometry. PD-L1, an immune checkpoint regulator, has been speculated to play a significant role in suppressing the immune system. It also helps tumor cells evade anti-tumor immunity. The expression of PD-L1 was induced by IFN-gamma stimulation. The anti-metastatic capacity of NTAX-44 was evaluated by in ovo chick embryo yolk sac membrane (YSM) angiogenesis assay. The cytocompatibility testing was done by testing the effect of NTAX-44 on the viability of normal human peripheral blood mononuclear cells (PBMC) by MTS assay. Results: NTAX-44 effectively inhibited the viability of MIA-Pa-Ca (IC50 4.63 +/- 1.16μg/ml for 48 hr and 0.50 +/- 0.63 for 72 hr of treatment); demonstrating the anti-proliferative activity of NTAX-44 against MIA-Pa-Ca-2 cell line. Furthermore, NTAX-44 at 25µg/ml concentration significantly inhibited IFN-gamma-induced PD-L1 expression in the MIA-Pa-Ca-2 cell line. Evaluation of the anti-metastatic potential of NTAX-44 exhibited around 40% inhibition in the number of quaternary blood vessels was observed on the treatment of YSM with NTAX-44 compared to vehicle control. It is noteworthy that the anti-angiogenic activity was comparable to that of Bevacizumab (Avastin®). The cytocompatibility testing revealed that it was well tolerated at a concentration up to 200μg/ml in PBMC cells. Conclusions: The preclinical data presented in this study suggests the potential of NTAX-44 to inhibit proliferation and, PD-L1 expression in MIA-Pa-Ca-2 cells and prevent angiogenesis in YSM. These properties along, with their good tolerability as indicated by cytocompatibility testing, are indicative of the potential role of NTAX-44 as an oral chemotherapeutic agent in the treatment of Pancreatic cancer. Though the preclinical studies performed on NTAX-44 are very promising but further clinical evaluation is warranted. Citation Format: Yogesh Bendale, Padma Shastri, Radha Poojari, Nandinee Khot, Surendra Nagare, Avinash Kadam. Anti-cancer activity of NTAX-44 (bioprocessed arsenic trioxide) on pancreatic cancer cell line [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-058.