Optimal Light Dose for hEGFR-Targeted Near-Infrared Photoimmunotherapy
Near-infrared photoimmunotherapy (NIR-PIT) is a newly developed cancer therapy that targets cancer cells using a monoclonal antibody-photon absorber conjugate (APC) that is bound to the target cell surface. Subsequent application of low levels of NIR light results in immediate cancer cell death. The...
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MDPI AG
2022-08-01
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| Online Access: | https://www.mdpi.com/2072-6694/14/16/4042 |
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| author | Hideyuki Furumoto Ryuhei Okada Takuya Kato Hiroaki Wakiyama Fuyuki Inagaki Hiroshi Fukushima Shuhei Okuyama Aki Furusawa Peter L. Choyke Hisataka Kobayashi |
| author_facet | Hideyuki Furumoto Ryuhei Okada Takuya Kato Hiroaki Wakiyama Fuyuki Inagaki Hiroshi Fukushima Shuhei Okuyama Aki Furusawa Peter L. Choyke Hisataka Kobayashi |
| author_sort | Hideyuki Furumoto |
| collection | DOAJ |
| description | Near-infrared photoimmunotherapy (NIR-PIT) is a newly developed cancer therapy that targets cancer cells using a monoclonal antibody-photon absorber conjugate (APC) that is bound to the target cell surface. Subsequent application of low levels of NIR light results in immediate cancer cell death. The anti-tumor effect of NIR-PIT in immunocompromised mice depends on immediate cancer cell death; therefore, the efficacy increases in a light-dose-dependent manner. However, NIR-PIT also induces a strong anti-tumor immune activation in immunocompetent mice that begins soon after therapy. Thus, it may be possible to reduce the light dose, which might otherwise cause local edema while maintaining therapeutic efficacy. In this study, we determined the optimal dose of NIR light in NIR-PIT based on a comparison of the therapeutic and adverse effects. Either one of two monoclonal antibodies (mAbs) against human epidermal growth factor receptor (hEGFR), Cetuximab or Panitumumab, were conjugated with a photo-absorbing chemical, IRDye700DX (IR700), and then injected in hEGFR-expressing mEERL (mEERL-hEGFR) tumor-bearing C57BL/6 immunocompetent mice or A431-GFP-luc tumor-bearing athymic immunocompromised mice. NIR light was varied between 0 to 100 J/cm<sup>2</sup> one day after administration of APC. In an immunocompromised mouse model, tumor growth was inhibited in a light-dose-dependent manner, yet extensive local edema and weight loss were observed at 100 J/cm<sup>2</sup>. On the other hand, in an immunocompetent mouse model using the mEERL-hEGFR cell line, maximal tumor response was achieved at 50 J/cm<sup>2</sup>, with a commensurate decrease in local edema. In this study, we show that a relatively low dose of NIR light is sufficient in an immunocompetent mouse model and avoids side effects seen with higher light doses required in immunocompetent mice. Thus, light dosing can be optimized in NIR-PIT based on the expected immune response. |
| first_indexed | 2024-03-09T04:37:59Z |
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| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T04:37:59Z |
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| spelling | doaj.art-542de9ef78114e4d84985fe5c51bc67d2023-12-03T13:25:44ZengMDPI AGCancers2072-66942022-08-011416404210.3390/cancers14164042Optimal Light Dose for hEGFR-Targeted Near-Infrared PhotoimmunotherapyHideyuki Furumoto0Ryuhei Okada1Takuya Kato2Hiroaki Wakiyama3Fuyuki Inagaki4Hiroshi Fukushima5Shuhei Okuyama6Aki Furusawa7Peter L. Choyke8Hisataka Kobayashi9Molecular Imaging Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USAMolecular Imaging Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USAMolecular Imaging Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USAMolecular Imaging Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USAMolecular Imaging Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USAMolecular Imaging Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USAMolecular Imaging Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USAMolecular Imaging Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USAMolecular Imaging Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USAMolecular Imaging Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USANear-infrared photoimmunotherapy (NIR-PIT) is a newly developed cancer therapy that targets cancer cells using a monoclonal antibody-photon absorber conjugate (APC) that is bound to the target cell surface. Subsequent application of low levels of NIR light results in immediate cancer cell death. The anti-tumor effect of NIR-PIT in immunocompromised mice depends on immediate cancer cell death; therefore, the efficacy increases in a light-dose-dependent manner. However, NIR-PIT also induces a strong anti-tumor immune activation in immunocompetent mice that begins soon after therapy. Thus, it may be possible to reduce the light dose, which might otherwise cause local edema while maintaining therapeutic efficacy. In this study, we determined the optimal dose of NIR light in NIR-PIT based on a comparison of the therapeutic and adverse effects. Either one of two monoclonal antibodies (mAbs) against human epidermal growth factor receptor (hEGFR), Cetuximab or Panitumumab, were conjugated with a photo-absorbing chemical, IRDye700DX (IR700), and then injected in hEGFR-expressing mEERL (mEERL-hEGFR) tumor-bearing C57BL/6 immunocompetent mice or A431-GFP-luc tumor-bearing athymic immunocompromised mice. NIR light was varied between 0 to 100 J/cm<sup>2</sup> one day after administration of APC. In an immunocompromised mouse model, tumor growth was inhibited in a light-dose-dependent manner, yet extensive local edema and weight loss were observed at 100 J/cm<sup>2</sup>. On the other hand, in an immunocompetent mouse model using the mEERL-hEGFR cell line, maximal tumor response was achieved at 50 J/cm<sup>2</sup>, with a commensurate decrease in local edema. In this study, we show that a relatively low dose of NIR light is sufficient in an immunocompetent mouse model and avoids side effects seen with higher light doses required in immunocompetent mice. Thus, light dosing can be optimized in NIR-PIT based on the expected immune response.https://www.mdpi.com/2072-6694/14/16/4042near-infrared photoimmunotherapylight doseEGFRside effects |
| spellingShingle | Hideyuki Furumoto Ryuhei Okada Takuya Kato Hiroaki Wakiyama Fuyuki Inagaki Hiroshi Fukushima Shuhei Okuyama Aki Furusawa Peter L. Choyke Hisataka Kobayashi Optimal Light Dose for hEGFR-Targeted Near-Infrared Photoimmunotherapy Cancers near-infrared photoimmunotherapy light dose EGFR side effects |
| title | Optimal Light Dose for hEGFR-Targeted Near-Infrared Photoimmunotherapy |
| title_full | Optimal Light Dose for hEGFR-Targeted Near-Infrared Photoimmunotherapy |
| title_fullStr | Optimal Light Dose for hEGFR-Targeted Near-Infrared Photoimmunotherapy |
| title_full_unstemmed | Optimal Light Dose for hEGFR-Targeted Near-Infrared Photoimmunotherapy |
| title_short | Optimal Light Dose for hEGFR-Targeted Near-Infrared Photoimmunotherapy |
| title_sort | optimal light dose for hegfr targeted near infrared photoimmunotherapy |
| topic | near-infrared photoimmunotherapy light dose EGFR side effects |
| url | https://www.mdpi.com/2072-6694/14/16/4042 |
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