Syngeneic Mouse Models of Oral Cancer Are Effectively Targeted by Anti-CD44-Based NIR-PIT.

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.