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Updated: Oct 14, 2025
Near Infrared Photoimmunotherapy for Mouse Models of Pleural Dissemination
Published on: February 9, 2021
HER2 targeting near-infrared photoimmunotherapy for a CDDP-resistant small-cell lung cancer
Kazuomi Takahashi1, Shunichi Taki1, Hirotoshi Yasui1
1Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Background:
Human epidermal growth factor receptor 2 (HER2) is tyrosine kinase receptor that belongs to the ErbB family and is overexpressed on the membrane surface of various cancer cells, including small cell lung cancer (SCLC); however, no HER2 targeted therapy for SCLC have yet been established. Near-infrared photoimmunotherapy (NIR-PIT) is a novel cancer therapy based on photo-absorber, IRDye-700DX (IR700), -antibody conjugates, and near-infrared (NIR) light.
Methods:
We used HER2-positive SCLC parental cell lines (SBC-3) and its chemoresistant cell lines, and examined therapeutic efficacy of HER2 targeting NIR-PIT using anti HER2 antibody trastuzumab.
Results:
We found that HER2 expression was upregulated on chemoresistant cell lines, especially cisplatin-resistance (SBC-3/CDDP). In vitro, the rate of cell death increased with the amount of NIR-light irradiation, and it was significantly higher in SBC-3/CDDP than in SBC-3. In vivo, tumor growth was more suppressed in SBC-3/CDDP group than in SBC-3 group, and survival period tended to be prolonged.
Conclusion:
In this study, we demonstrated that HER2 targeting NIR-PIT using trastuzumab is promising therapy for HER2-positive SCLC, and is more effective when HER2 expression is upregulated due to CDDP resistance, suggesting that the HER2 expression level positively corelated with the efficacy of NIR-PIT.
Insights
Near-infrared photoimmunotherapy (NIR-PIT) targeting human epidermal growth factor receptor 2 (HER2) shows promise for small cell lung cancer (SCLC). This therapy is more effective in chemoresistant SCLC with higher HER2 expression.
Area of Science:
- Oncology
- Biotechnology
- Immunotherapy
Background:
- Human epidermal growth factor receptor 2 (HER2) is overexpressed in various cancers, including small cell lung cancer (SCLC), but lacks targeted therapies.
- Near-infrared photoimmunotherapy (NIR-PIT) utilizes a photo-absorber (IRDye-700DX) and antibody conjugates activated by near-infrared light.
Purpose of the Study:
- To evaluate the therapeutic efficacy of HER2-targeting NIR-PIT using trastuzumab in HER2-positive SCLC.
- To investigate the correlation between HER2 expression levels and NIR-PIT effectiveness, particularly in chemoresistant SCLC.
Main Methods:
- Utilized HER2-positive SCLC cell lines (SBC-3) and cisplatin-resistant variants (SBC-3/CDDP).
- Administered HER2-targeting NIR-PIT with trastuzumab and varying doses of NIR light.
- Assessed in vitro cell death rates and in vivo tumor suppression and survival periods.
Main Results:
- HER2 expression was notably upregulated in cisplatin-resistant SCLC cells (SBC-3/CDDP).
- In vitro, NIR-PIT significantly increased cell death in SBC-3/CDDP compared to SBC-3, correlating with NIR light dosage.
- In vivo studies showed enhanced tumor growth suppression and prolonged survival in the SBC-3/CDDP group.
Conclusions:
- HER2-targeting NIR-PIT with trastuzumab is a promising therapeutic strategy for HER2-positive SCLC.
- The efficacy of NIR-PIT is positively correlated with HER2 expression levels, especially in cases of acquired cisplatin resistance.
