Journal
CANCER MEDICINE
Volume 10, Issue 24, Pages 8808-8819Publisher
WILEY
DOI: 10.1002/cam4.4381
Keywords
chemotherapy-resistant; cisplatin; HER2; near-infrared photoimmunotherapy; small-cell lung cancer
Categories
Funding
- Japan Science and Technology Agency
- JSPS [18K15923, 21K07217]
- AMED hashiwatashi seeds A
- Uehara Memorial Foundation
- CREST (JST)
- Core Research for Evolutional Science and Technology
- FOREST-Souhatsu
- Grants-in-Aid for Scientific Research [21K07217, 18K15923] Funding Source: KAKEN
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The study demonstrates that HER2-targeted NIR-PIT may be a promising treatment for HER2-positive SCLC, particularly when HER2 expression is upregulated due to cisplatin resistance, indicating a positive correlation between HER2 expression level and NIR-PIT efficacy.
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.
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