Research Papers:
Immunogenic cancer cell death selectively induced by near infrared photoimmunotherapy initiates host tumor immunity
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Abstract
Mikako Ogawa1,7,*, Yusuke Tomita2,*, Yuko Nakamura3, Min-Jung Lee2, Sunmin Lee2, Saori Tomita2, Tadanobu Nagaya3, Kazuhide Sato3, Toyohiko Yamauchi4, Hidenao Iwai4, Abhishek Kumar5, Timothy Haystead6, Hari Shroff5, Peter L. Choyke3, Jane B. Trepel2, Hisataka Kobayashi3
1Medical Photonics Research Center, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan
2Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA
3Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA
4Central Research Laboratory, Hamamatsu Photonics K. K., Hamamatsu 434-8601, Japan
5Section on High Resolution Optical Imaging, NIBIB/NIH, Bethesda, MD 20892, USA
6Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA
7Laboratory for Bioanalysis and Molecular Imaging, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
*Co-first author
Correspondence to:
Hisataka Kobayashi, email: [email protected]
Keywords: near infrared photoimmunotherapy, immunogenic cell death
Received: October 12, 2016 Accepted: December 13, 2016 Published: January 02, 2017
ABSTRACT
Immunogenic cell death (ICD) is a form of cell death that activates an adaptive immune response against dead-cell-associated antigens. Cancer cells killed via ICD can elicit antitumor immunity. ICD is efficiently induced by near-infrared photo-immunotherapy (NIR-PIT) that selectively kills target-cells on which antibody-photoabsorber conjugates bind and are activated by NIR light exposure. Advanced live cell microscopies showed that NIR-PIT caused rapid and irreversible damage to the cell membrane function leading to swelling and bursting, releasing intracellular components due to the influx of water into the cell. The process also induces relocation of ICD bio markers including calreticulin, Hsp70 and Hsp90 to the cell surface and the rapid release of immunogenic signals including ATP and HMGB1 followed by maturation of immature dendritic cells. Thus, NIR-PIT is a therapy that kills tumor cells by ICD, eliciting a host immune response against tumor.
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