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Cancer cell–selective in vivo near infrared photoimmunotherapy targeting specific membrane molecules

Nature Medicine volume 17, pages 1685–1691 (2011)Cite this article

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Abstract

Three major modes of cancer therapy (surgery, radiation and chemotherapy) are the mainstay of modern oncologic therapy. To minimize the side effects of these therapies, molecular-targeted cancer therapies, including armed antibody therapy, have been developed with limited success. In this study, we have developed a new type of molecular-targeted cancer therapy, photoimmunotherapy (PIT), that uses a target-specific photosensitizer based on a near-infrared (NIR) phthalocyanine dye, IR700, conjugated to monoclonal antibodies (mAbs) targeting epidermal growth factor receptors. Cell death was induced immediately after irradiating mAb-IR700–bound target cells with NIR light. We observed in vivo tumor shrinkage after irradiation with NIR light in target cells expressing the epidermal growth factor receptor. The mAb-IR700 conjugates were most effective when bound to the cell membrane and produced no phototoxicity when not bound, suggesting a different mechanism for PIT as compared to conventional photodynamic therapies. Target-selective PIT enables treatment of cancer based on mAb binding to the cell membrane.

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Figure 1: mAb-IR700 PIT in physics-based cancer therapies.
Figure 2: Target-specific cell death in response to Tra-IR700–mediated PIT in 3T3-HER2 cells.
Figure 3: Target-specific cell death in response to Pan-IR700–mediated PIT in epidermal growth factor receptor (EGFR)-expressing A431 cells.
Figure 4: Tra-IR700–mediated PIT for co-cultured cells either expressing or not expressing HER2.
Figure 5: Pan-IR700–mediated PIT for HER1-expressing tumors in vivo.

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Acknowledgements

This research was supported by the Intramural Research Program of the US National Institutes of Health, National Cancer Institute, Center for Cancer Research. We would like to thank C. Regino, T. Hirano and C. Paik for their technical support.

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Authors and Affiliations

  1. Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, US National Institutes of Health, Bethesda, Maryland, USA

    Makoto Mitsunaga, Mikako Ogawa, Nobuyuki Kosaka, Lauren T Rosenblum, Peter L Choyke & Hisataka Kobayashi

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  1. Makoto Mitsunaga
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  2. Mikako Ogawa
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  3. Nobuyuki Kosaka
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  4. Lauren T Rosenblum
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  5. Peter L Choyke
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  6. Hisataka Kobayashi
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Contributions

M.M. conducted experiments, performed analysis and wrote the manuscript. M.O., N.K. and L.T.R. conducted experiments and performed analysis. P.L.C. wrote the manuscript and supervised the project. H.K. planned and initiated the project, designed and conducted experiments, wrote the manuscript and supervised the project.

Corresponding author

Correspondence to Hisataka Kobayashi.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–8 and Supplementary Methods (PDF 878 kb)

Supplementary Video 1a

Real-time observation of Tra-IR700 mediated phototoxic cell death. (MOV 443 kb)

Supplementary Video 1b

Real-time observation of Tra-IR700 mediated phototoxic cell death. (MOV 347 kb)

Supplementary Video 2

Target specific phototoxicity in response to Tra-IR700 mediated photoimmunotherapy in vitro. (MOV 374 kb)

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Mitsunaga, M., Ogawa, M., Kosaka, N. et al. Cancer cell–selective in vivo near infrared photoimmunotherapy targeting specific membrane molecules. Nat Med 17, 1685–1691 (2011). https://doi.org/10.1038/nm.2554

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