Abstract B083: Lectin-based photoimmunotherapy targeting cell surface glycans for pancreatic cancer

Abstract

Abstract Introduction: We have previously demonstrated that fucosylated glycans (H type-3 motifs) are expressed in pancreatic cancers and a recombinant lectin, called rBC2LCN, binds to these glycans specifically (Shimomura O, Oda T, et al: Mol Cancer Ther 2018). This rBC2LCN lectin has development potential for payload delivery to pancreatic cancer cell surfaces. However, the lectin has cross reactivity to noncancerous cells, including renal tubular epithelial cells. Therefore, for the purpose of targeting cancer cells more specifically, we have applied this lectin-based carrier system for near-infrared photoimmunotherapy (NIR-PIT). This lectin-based PIT (Lec-PIT), using a lectin-photoabsorber conjugate (BC2-IR700), successfully showed anti-tumor effect upon NIR-light exposure in in vivo mouse model (Kuroda et al: AACR Annual Meeting 2022). In this study, we assessed biodistribution of BC2-IR700 and investigated that Lec-PIT minimized off-target toxicity by shielding of intraperitoneal organs from near-infrared light in orthotopic model of pancreatic cancer. Material and Methods: BC2-IR700 was synthesized by conjugating rBC2LCN lectin with IR700 NHS ester. Capan-1, an H type-3-positive human pancreatic cancer cell line, was used as a model which is bound by rBC2LCN lectin. Capan-1 was transfected with a GFP-luciferase-encoding lentivirus, which was abbreviated as Capan-1-GFP-luc. We used Capan-1-GFP-luc cells for engraftment into nude mice to visualize orthotopic pancreatic tumors by luciferase bioluminescence. Lec-PIT was performed by exposing to NIR light (100 J/cm2) at 6 h following BC2-IR700 intravenous administration (20 μg/mouse). Results: Ex vivo examination was performed to assess the biodistribution of BC2-IR700 at 6 hours after administration. Each organ and tumor were resected from a pancreatic cancer xenograft mouse and imaged using IVIS Spectrum. A high fluorescence intensity was observed in tumor, kidney and liver. For Lec-PIT in an orthotopic model of pancreatic cancer, NIR light was directed at the tumor intraperitoneally under laparotomy with the rest of the organs shielded by aluminum foil. Lec-PIT group showed significantly lower bioluminescence during the experimental period (P < 0.01 vs control group). No hematological parameters, including CRE, AST and ALT, differed significantly between the control and Lec-PIT groups. Additionally, histological examination of intraperitoneal organs collected from the Lec-PIT group showed no abnormal findings. Conclusions: We described that Lec-PIT is safe and any unintended damage due to accumulation of BC2-IR700 can be mitigated by shielding these areas with NIR-reflective material. This novel PIT targeting cell surface glycans could be a promising therapeutic strategy for the treatment of pancreatic cancer. Citation Format: Yukihito Kuroda, Osamu Shimomura, Hiromitsu Nakahashi, Yoshihiro Miyazaki, Takahito Nakajima, Hiroaki Tateno, Tatsuya Oda. Lectin-based photoimmunotherapy targeting cell surface glycans for pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr B083.