Abstract 270: Enhanced anti-tumor effect and tolerance of novel irinotecan (sn-38) nanoparticle with double core-shell micelle technology

Abstract

Abstract SN-38 is a potent active metabolite of irinotecan with wide range of anti-tumor effect acknowledged in pancreatic, ovarian, lung, breast cancer models as well as colorectal cancer. Studies suggest irinotecan has extremely low solubility in biological fluid, and since irinotecan is a prodrug with the low conversion rate to the pharmaceutically active form, SN-38, the indication is limited to colorectal cancer. SN Bioscience has developed stable and safe SN-38 nano-particle injection (SNB-101) with approved biopolymers with double core-shell micelle technology and conducted preclinical studies in various tumor models for the assessment of efficacy. Outcomes suggest reduction in the tumor weight and inhibition of the growth rate in the every human tumor cell lines, revealing that 20 mg/kg (as SN-38) of SNB-101 is more effective in reducing tumor size than its comparative substance (Irinotecan HCl, 50 mg/kg). The results indicate the MTD of SNB-101 could be increased by least 2.67 folds through new drug delivery system by nano-particle injection. To further investigate the antitumor activity of SNB-101, we have applied the therapy in combination with different kinds of medications in the additional models. First, we have examined synergistic antitumor activity of SNB-101 in combined therapy with Docetaxel in various mouse xenograft models of gastric cancer (Hs746T), breast cancer (MDA-MB-231), and lung cancer (A549). As results, we have established the combination use of SNB-101 plus Docetaxel had significantly greater antitumor activity against all the monotherapy control groups. Second, we have continued to investigate the advantages of combination treatment of SNB-101 plus Radiotherapy (5Gy) in mice xenograft derived with SCLC (NCI-H69) and colorectal cancer (HCT116). From these studies, promising outcome of antitumor action was also noted, recapitulating excellent therapeutic effect of SNB-101 alone and in combination with Radiotherapy against lung cancer and colorectal cancer cells. Furthermore, an additional study with combination of SNB-101 plus an anti-vascular endothelial growth factor humanized monoclonal antibody (Bevacizumab) showed significantly stronger anti-tumor activities against the HT-29 xenograft model than did the monotherapy with either agent. As the addition of Bevacizumab to SNB-101 monotherapy is associated with profound inhibition of HT-29 tumor growth progression, the consistent reduction in tumor weights was also observed. Although tolerability of the substance in clinical studies is well known, there are some limitations in correlating the results of pre-clinical models to in-depth comprehension of human model; thus, we hope to further investigate the pharmacological action of SNB-101 in new regimens and indications in the next step - First in Human trial. Citation Format: Jong Oh Kim, Eun Kyung Choi, Seong Yun Jeong, Jung Jin Hwang, Eun Sung Jun, Jae-Min Kim, Hong-Mei Zheng, Younghwan Park, Siyoung Jung. Enhanced anti-tumor effect and tolerance of novel irinotecan (sn-38) nanoparticle with double core-shell micelle technology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 270.