Abstract 5328: Near-infrared photoimmunotherapy for pancreatic cancer: Targeting cell surface glycans using lectin-photoabsorber conjugate (LPC)

Abstract

Abstract Introduction: Since protein targets in cancer therapy largely have been explored, glycans would be attractive alternative targets. We had previously discovered a fucosylated glycan epitope highly expressed on pancreatic cancer cells, and a lectin probe called rBC2LCN, which can be used as a specific targeting bullet to this glycan (Shimomura O, Oda T, et al: Mol Cancer Ther 2018). We now then hypothesized that, this lectin-based cancer-targeting strategies should be reasonably applicable to near-infrared photoimmunotherapy (NIR-PIT). NIR-PIT have already developed using a conjugate of a photoabsorber, IRdye700DX (IR700), and a monoclonal antibody which recognizes protein antigens on the target cells. In this study, we firstly developed a lectin-photoabsorber conjugate (BC2-IR700) and investigated a new cancer therapy targeting cancer cell surface glycans. Material and Methods: We developed BC2-IR700 by conjugation of rBC2LCN lectin with IR700 NHS ester. A pancreatic cancer cell line Capan-1 was used as a model which is bound by rBC2LCN. The cytotoxic effect of NIR-PIT with BC2-IR700 was first evaluated in vitro. We then evaluated the anti-cancer effect of BC2-IR700 in vivo using pancreatic cancer xenograft mice including subcutaneous tumor model. Results: The product of BC2-IR700 was confirmed by SDS-PAGE, that showed reasonable 16KDa sharp band with clear fluorescence intensity. After incubation with BC2-IR700, Capan-1 cells showed high fluorescence signal, which was confirmed with flow cytometry and fluorescence microscopy. BC2-IR700 was detected on the cell surface of Capan-1 after incubation for 1h. Immediately after exposure to NIR light, the cell death of Capan-1 was induced and the cytotoxicity significantly increased in a light-dose-dependent manner. After intravenous administration of BC2-IR700 into pancreatic cancer xenograft mice, BC2-IR700 was observed in vivo fluorescence imaging to be accumulated in tumor. NIR-PIT was performed by exposing to NIR light (100 J/cm2) at 6 h following BC2-IR700 intravenous administration (20 μg/mice). Tumor growth was significantly inhibited in the NIR-PIT treatment group compared with the other control groups such as no treatment, BC2-IR700 only, and NIR light exposure only (P < 0.05). Conclusions: The lectin-photoabsorber conjugate, BC2-IR700, was able to be sufficiently applied for NIR-PIT in in vivo mouse model. The novel NIR-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, Tomoaki Furuta, Yoshihiro Miyazaki, Takahito Nakajima, Hiroaki Tateno, Tatsuya Oda. Near-infrared photoimmunotherapy for pancreatic cancer: Targeting cell surface glycans using lectin-photoabsorber conjugate (LPC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5328.