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Background <p>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.</p> Methods <p>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.</p> Results <p>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.</p> Conclusions <p>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.</p>

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CD44-targeted near-infrared photoimmunotherapy shows potent anti-tumor effects in an orthotopic lung cancer model

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年8月1日

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  • Hiroshi Yamasaki,
  • Kohei Nakajima,
  • Hideki Ujiie,
  • Ryohei Chiba,
  • Haruhiko Shiiya,
  • Kazuto Ohtaka,
  • Aki Fujiwara-Kuroda,
  • Masato Aragaki,
  • Kanako C. Hatanaka,
  • Yutaka Hatanaka,
  • Mikako Ogawa,
  • Tatsuya Kato

摘要

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.