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Updated: Feb 22, 2026
Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019
Syngeneic Mouse Models of Oral Cancer Are Effectively Targeted by Anti-CD44-Based NIR-PIT
Tadanobu Nagaya1, Yuko Nakamura1, Shuhei Okuyama1
1Molecular Imaging Program, Center for Cancer Research, NCI, NIH, Bethesda, Maryland.
Abstract:
Oral cavity squamous cell carcinoma (OSCC) is considered one of the most aggressive subtypes of cancer. Anti-CD44 monoclonal antibodies (mAb) are a potential therapy against CD44 expressing OSCC; however, to date the therapeutic effects have been disappointing. Here, a new cancer treatment is described, near-infrared photoimmunotherapy (NIR-PIT), that uses anti-CD44 mAbs conjugated to the photoabsorber IR700DX. This conjugate is injected into mice harboring one of three CD44 expressing syngeneic murine oral cancer cell (MOC) lines, MOC1 (immunogenic), MOC2 mKate2 (moderately immunogenic), and MOC2-luc (poorly immunogenic). Binding of the anti-CD44-IR700 conjugate was shown to be specific and cell-specific cytotoxicity was observed after exposure of the cells to NIR light in vitro The anti-CD44-IR700 conjugate, when assessed in vivo, demonstrated deposition within the tumor with a high tumor-to-background ratio. Tumor-bearing mice were separated into four cohorts: no treatment; 100 microg of anti-CD44-IR700 i.v. only; NIR light exposure only; and 100 microg of anti-CD44-IR700 i.v. with NIR light exposure. NIR-PIT therapy, compared with the other groups, significantly inhibited tumor growth and prolonged survival in all three cell model systems. In conclusion, these data reveal that anti-CD44 antibodies are suitable as mAb-photoabsorber conjugates for NIR-PIT in MOC cells.Implications: This study using syngeneic mouse models, which better model the disease in humans than conventional xenografts, suggests that NIR-PIT with anti-CD44-IR700 is a potential candidate for the treatment of OSCC. Mol Cancer Res; 15(12); 1667-77. ©2017 AACR.
Insights
Near-infrared photoimmunotherapy (NIR-PIT) using anti-CD44 antibody-IR700DX conjugates shows promise for treating oral cavity squamous cell carcinoma (OSCC). This novel cancer treatment effectively inhibited tumor growth and improved survival in preclinical models.
Area of Science:
- Oncology
- Immunotherapy
- Biotechnology
Background:
- Oral cavity squamous cell carcinoma (OSCC) is an aggressive cancer with limited therapeutic options.
- Current anti-CD44 monoclonal antibody (mAb) therapies for OSCC have shown disappointing results.
- CD44 is a cell surface marker frequently overexpressed in OSCC, making it a target for therapy.
Purpose of the Study:
- To evaluate the efficacy of a novel near-infrared photoimmunotherapy (NIR-PIT) utilizing anti-CD44 mAb conjugated to the photoabsorber IR700DX for OSCC treatment.
- To assess the specificity, cytotoxicity, and in vivo tumor targeting of the anti-CD44-IR700 conjugate.
- To determine the therapeutic effect of NIR-PIT on tumor growth inhibition and survival in preclinical OSCC models.
Main Methods:
- Development of anti-CD44 mAb conjugated to IR700DX photoabsorber.
- In vitro assessment of conjugate binding specificity and cell-specific cytotoxicity upon NIR light exposure in CD44-expressing murine oral cancer (MOC) cell lines.
- In vivo evaluation of conjugate tumor deposition and anti-tumor efficacy in MOC tumor-bearing mice treated with varying combinations of conjugate and NIR light.
Main Results:
- The anti-CD44-IR700 conjugate demonstrated specific binding and induced cell-specific cytotoxicity in vitro.
- In vivo studies showed high tumor-to-background ratio deposition of the conjugate within tumors.
- NIR-PIT significantly inhibited tumor growth and prolonged survival across three different MOC models compared to control groups.
Conclusions:
- Anti-CD44 antibodies are suitable for developing mAb-photoabsorber conjugates for NIR-PIT in OSCC.
- NIR-PIT with anti-CD44-IR700 represents a promising therapeutic strategy for OSCC.
- Syngeneic mouse models suggest NIR-PIT is a potential candidate for treating human OSCC.
