Treatment of Pancreatic Cancer Using Near-Infrared Photoimmunotherapy Targeting Cancer-Associated Fibroblasts in Combination with Anticancer Chemotherapeutic Drug

Hiroki Yonemura; Masaki Kuwatani; Kohei Nakajima; Atsushi Masamune; Mikako Ogawa; Naoya Sakamoto

doi:10.3390/cancers17091584

Treatment of Pancreatic Cancer Using Near-Infrared Photoimmunotherapy Targeting Cancer-Associated Fibroblasts in Combination with Anticancer Chemotherapeutic Drug

Cancers (Basel). 2025 May 7;17(9):1584. doi: 10.3390/cancers17091584.

Authors

Hiroki Yonemura¹, Masaki Kuwatani¹, Kohei Nakajima², Atsushi Masamune³, Mikako Ogawa^{2

4}, Naoya Sakamoto¹

Affiliations

¹ Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, North 15, West 7, Kita-ku, Sapporo 060-8648, Hokkaido, Japan.
² Laboratory of Bioanalysis and Molecular Imaging, Graduate School of Pharmaceutical Sciences, Hokkaido University, North 12, West 6, Kita-ku, Sapporo 060-0812, Hokkaido, Japan.
³ Division of Gastroenterology, Tohoku University Hospital, Seiryocho1-1, Aoba-ku, Sendai 980-8574, Miyagi, Japan.
⁴ Institute for Chemical Reaction Design and Discovery (WPI-ICReDD), Hokkaido University, North 21, West 10, Kita-ku, Sapporo 001-0021, Hokkaido, Japan.

Abstract

Background: Pancreatic ductal adenocarcinoma (PDAC), which has a poor prognosis, involves an overabundance of fibroblasts and extracellular matrix. Cancer-associated fibroblasts (CAFs) are critical for providing structural support by secreting soluble factors and extracellular matrix proteins into the stroma. We assessed the potential of near-infrared photoimmunotherapy (NIR-PIT) targeting CAFs in PDAC. Methods: PDAC cells (Capan-1 and SUIT-2) and CAFs (hPSC-5) were used. Anti-human fibroblast activation protein (FAP)/podoplanin (PDPN) antibodies were used to bind to CAFs and conjugates with the specific photosensitizer IRDye^®700DX (IR700) to investigate the effects of NIR-PIT. Thereafter, BALB/c Slc-nu/nu mice were transplanted with Capan-1 and/or CAFs and treated with gemcitabine (GEM) with or without NIR-PIT. Results: The binding rate of anti-FAP antibody-AlexaFluor^®488 conjugate to hPSC-5 cells was high, whereas that of the anti-PDPN antibody-conjugate was not. The incubation of anti-FAP antibody-IR700 conjugate (αFAP-IR700) with hPSC-5 cells for 3 h led to maximal fluorescence on the surface of hPSC-5 cells. When NIR-PIT with αFAP-IR700 was performed in the co-culture group of Capan-1 and hPSC-5 cells, the proliferative capacity of Capan-1 cells decreased to the same level as that when Capan-1 cells were cultured alone (p < 0.05). In vivo, compared with the GEM group, the NIR-PIT with the GEM group showed a significant reduction in the tumor volume (day 28: 79 vs. 382 mm³, p < 0.05). Tumor volumes in the NIR-PIT group were not reduced compared with those in the control group. Conclusions: Combining NIR-PIT with conventional chemotherapy to target CAFs may enhance the anticancer effects on PDAC.

Keywords: cancer-associated fibroblast; combination therapy; near-infrared photo-immunotherapy; pancreatic ductal cancer.

Abstract

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