CD44-targeted near-infrared photoimmunotherapy shows potent anti-tumor effects in an orthotopic lung cancer model.
5 affiliations
- 1Department of Thoracic Surgery, Hokkaido University Hospital, N14W5, Kita-Ku, Sapporo, Hokkaido, 060-8648, Japan.
- 2Laboratory of Bioanalysis and Molecular Imaging, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
- 3Division of Thoracic Surgery, Department of Surgery, Faculty of Medicine, Kindai University, Osaka, Japan.
- 4Center for Development of Advanced Diagnostics, Hokkaido University Hospital, Sapporo, Japan.
- 5Department of Thoracic Surgery, Hokkaido University Hospital, N14W5, Kita-Ku, Sapporo, Hokkaido, 060-8648, Japan. [email protected].
Abstract
Background
Lung cancer continues to be associated with a dismal prognosis, despite the recent development of multiple therapeutic modalities. Consequently, there remains an urgent need for the advancement of novel and more efficacious treatment strategies. Cluster of Differentiation 44 (CD44), a cell surface marker associated with cancer stem cells, has been implicated in tumor progression, metastasis, and resistance to therapy, thereby representing a compelling target for oncologic intervention. Near-infrared photoimmunotherapy (NIR-PIT) is an emerging cancer treatment modality that integrates the high specificity of monoclonal antibodies with cytotoxic effects induced by a photosensitizer upon exposure to NIR light. In the present study, we evaluated the therapeutic efficacy of CD44-targeted NIR-PIT utilizing an orthotopic lung cancer mouse model established via transtracheal tumor cell injection, which more faithfully recapitulates the tumor microenvironment compared to conventional subcutaneous models.Methods
An antibody-photoabsorber conjugate was synthesized by conjugating an anti-CD44 monoclonal antibody (IM7) with IRDye700DX (IR700). The cytotoxic effects of CD44-targeted NIR-PIT were assessed in vitro using CD44-expressing lung cancer cell lines. Therapeutic efficacy was subsequently evaluated in an orthotopic lung cancer mouse model established by transtracheal injection of tumor cells. Tumor progression was monitored by bioluminescence imaging, and survival and histopathological changes were analyzed following treatment.Results
In vitro experiments employing CD44-expressing cell lines demonstrated that CD44-targeted NIR-PIT induces cytotoxicity in a light dose-dependent manner. The in vivo therapeutic efficacy was subsequently assessed using the orthotopic lung cancer mouse model. Following CD44-targeted NIR-PIT, bioluminescence imaging revealed a marked reduction in tumor burden, accompanied by an exploratory difference in survival in a small cohort. Histological analysis further demonstrated tumor cell elimination and intratumoral hemorrhage in the treated lesions.Conclusions
CD44-targeted NIR-PIT demonstrated potent antitumor activity in an orthotopic lung cancer model. These findings support the potential clinical translation of CD44-targeted NIR-PIT as a novel therapeutic strategy for lung cancer. Further studies are warranted to optimize clinically feasible light-delivery methods and establish the long-term safety of this approach.
Related
- Complementary cytotoxicity of GD2-targeted photoimmunotherapy and 5-aminolevulinic acid photodynamic therapy in neuroblastoma and osteosarcoma
- Clinical outcomes of near-infrared photoimmunotherapy according to immune checkpoint inhibitor timing and treatment sequence: a multicenter retrospective study
- 897 Pre-clinical characterization of PEC3001, a PD-1 targeted IL-2Rα-active IL-2 immunocytokine with potent anti-tumor activity and a favorable safety profile
- Early Detection of Metastasis-Hypoxia Temporal Alterations in Orthotopic Breast Cancer Using Photoacoustic and Deuterium Metabolic Imaging: In Vivo Assessments.
- CD73-targeted CAR-NK cell therapy displays potent antitumor activity and translational potential in relapsed/refractory lung adenocarcinoma.
BibTeX
@article{yamasaki2026cd44targeted,
title = {{CD44-targeted near-infrared photoimmunotherapy shows potent anti-tumor effects in an orthotopic lung cancer model.}},
author = {Hiroshi Yamasaki and Kohei Nakajima and Hideki Ujiie and Ryohei Chiba and Haruhiko Shiiya and Kazuto Ohtaka and Aki Fujiwara-Kuroda and Masato Aragaki and Kanako C Hatanaka and Yutaka Hatanaka and Mikako Ogawa and Tatsuya Kato},
journal = {BMC cancer},
year = {2026},
month = aug,
doi = {10.1186/s12885-026-16652-5},
url = {https://europepmc.org/article/MED/42958098},
note = {CC BY},
}
RIS
TY - JOUR
TI - CD44-targeted near-infrared photoimmunotherapy shows potent anti-tumor effects in an orthotopic lung cancer model.
AU - Hiroshi Yamasaki
AU - Kohei Nakajima
AU - Hideki Ujiie
AU - Ryohei Chiba
AU - Haruhiko Shiiya
AU - Kazuto Ohtaka
AU - Aki Fujiwara-Kuroda
AU - Masato Aragaki
AU - Kanako C Hatanaka
AU - Yutaka Hatanaka
AU - Mikako Ogawa
AU - Tatsuya Kato
PY - 2026
DA - 2026/08/01
JO - BMC cancer
DO - 10.1186/s12885-026-16652-5
UR - https://europepmc.org/article/MED/42958098
AB - Background Lung cancer continues to be associated with a dismal prognosis, despite the recent development of multiple therapeutic modalities. Consequently, there remains an urgent need for the advancement of novel and more efficacious treatment strategies. Cluster of Differentiation 44 (CD44), a cell surface marker associated with cancer stem cells, has been implicated in tumor progression, metastasis, and resistance to therapy, thereby representing a compelling target for oncologic intervention. Near-infrared photoimmunotherapy (NIR-PIT) is an emerging cancer treatment modality that integrates the high specificity of monoclonal antibodies with cytotoxic effects induced by a photosensitizer upon exposure to NIR light. In the present study, we evaluated the therapeutic efficacy of CD44-targeted NIR-PIT utilizing an orthotopic lung cancer mouse model established via transtracheal tumor cell injection, which more faithfully recapitulates the tumor microenvironment compared to conventional subcutaneous models.Methods An antibody-photoabsorber conjugate was synthesized by conjugating an anti-CD44 monoclonal antibody (IM7) with IRDye700DX (IR700). The cytotoxic effects of CD44-targeted NIR-PIT were assessed in vitro using CD44-expressing lung cancer cell lines. Therapeutic efficacy was subsequently evaluated in an orthotopic lung cancer mouse model established by transtracheal injection of tumor cells. Tumor progression was monitored by bioluminescence imaging, and survival and histopathological changes were analyzed following treatment.Results In vitro experiments employing CD44-expressing cell lines demonstrated that CD44-targeted NIR-PIT induces cytotoxicity in a light dose-dependent manner. The in vivo therapeutic efficacy was subsequently assessed using the orthotopic lung cancer mouse model. Following CD44-targeted NIR-PIT, bioluminescence imaging revealed a marked reduction in tumor burden, accompanied by an exploratory difference in survival in a small cohort. Histological analysis further demonstrated tumor cell elimination and intratumoral hemorrhage in the treated lesions.Conclusions CD44-targeted NIR-PIT demonstrated potent antitumor activity in an orthotopic lung cancer model. These findings support the potential clinical translation of CD44-targeted NIR-PIT as a novel therapeutic strategy for lung cancer. Further studies are warranted to optimize clinically feasible light-delivery methods and establish the long-term safety of this approach.
SN - 1471-2407
ER -