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Selection of antibody and light exposure regimens alters therapeutic effects of EGFR-targeted near-infrared photoimmunotherapy

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Abstract

Near-infrared photoimmunotherapy (NIR-PIT) is a cell-specific cancer therapy that uses an antibody-photoabsorber (IRDye700DX, IR700) conjugate (APC) and NIR light. Intravenously injected APC binds the target cells, and subsequent NIR light exposure induces immunogenic cell death only in targeted cells. Panitumumab and cetuximab are antibodies that target human epidermal growth factor receptor (hEGFR) and are suitable for NIR-PIT. In athymic nude mouse models, panitumumab-based NIR-PIT showed superior therapeutic efficacy compared to cetuximab-based NIR-PIT because of the longer half-life of panitumumab-IR700 (pan-IR700) compared with cetuximab-IR700 (cet-IR700). Two light exposures on two consecutive days have also been shown to induce superior effects compared to a single light exposure in the athymic nude mouse model. However, the optimal regimen has not been assessed in immunocompetent mice. In this study, we compared panitumumab and cetuximab in APCs for NIR-PIT, and single and double light exposures using a newly established hEGFR-expressing cancer cell line derived from immunocompetent C57BL/6 mice (mEERL-hEGFR cell line). Fluorescence imaging showed that the decline of pan-IR700 was slower than cet-IR700 confirming a longer clearance time. Among all the combinations tested, mice receiving pan-IR700 and double light exposure showed the greatest tumor growth inhibition. This group was also shown to activate CD8+ T lymphocytes in lymph nodes and accumulate CD8+ T lymphocytes to a greater extent within the tumor compared with the control group. These results showed that APCs with longer half-life and double light exposure lead to superior outcomes in cancer cell-targeted NIR-PIT in an immunocompetent mouse model.

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Funding

This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research (ZIA BC011513). F.I. was also supported with a grant from National Center for Global Health and Medicine Research Institute, Tokyo, Japan.

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Authors and Affiliations

  1. Molecular Imaging Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 10, Room B3B69, MSC 1088, 10 Center Drive, Bethesda, MD, 20892, USA

    Ryuhei Okada, Takuya Kato, Aki Furusawa, Fuyuki Inagaki, Hiroaki Wakiyama, Daiki Fujimura, Shuhei Okuyama, Hideyuki Furumoto, Hiroshi Fukushima, Peter L. Choyke & Hisataka Kobayashi

Authors
  1. Ryuhei Okada
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  2. Takuya Kato
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  3. Aki Furusawa
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  4. Fuyuki Inagaki
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  5. Hiroaki Wakiyama
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  6. Daiki Fujimura
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  7. Shuhei Okuyama
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  8. Hideyuki Furumoto
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  9. Hiroshi Fukushima
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  10. Peter L. Choyke
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  11. Hisataka Kobayashi
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Contributions

R.O. mainly designed and conducted experiments, performed analysis and wrote the manuscript; T.K., A.F., F.I., H.W., D.F., S.O., H.F., and H.F. performed experiments and analysis; P.L.C. wrote the manuscript and supervised the project; and H.K. planned and initiated the project, designed and conducted experiments, wrote the manuscript, and supervised the entire project.

Corresponding author

Correspondence to Hisataka Kobayashi.

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The authors have no conflict of interest to disclose.

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Animal studies were approved by the local Animal Care and Use Committee (MIP-003; project number P183735).

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Okada, R., Kato, T., Furusawa, A. et al. Selection of antibody and light exposure regimens alters therapeutic effects of EGFR-targeted near-infrared photoimmunotherapy. Cancer Immunol Immunother 71, 1877–1887 (2022). https://doi.org/10.1007/s00262-021-03124-x

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  • DOI: https://doi.org/10.1007/s00262-021-03124-x

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