Photoimmunotherapy has been established as a potential and highly selective cancer therapy against EGFR, HER2, PSMA, and CD25 postive tumors. All targeted cells are killed by necrotic cell death after irreversible damage to the cell membrane immediately after exposure to near infrared light at 690 nm. We are currently investigating precise mechanisms of membrane damage. We are also expanding the repertoire of potential target molecules to include MUC1, CEA, laminine, GPC3, mesothelin, etc. by obtaining new antibodies for covering wider varieties of cancer. Additionally, we are also establishing novel non-invasive imaging methods to diagnose the therapeutic effects of PIT because necrotic cell killing induced by PIT is a very rapid process and cells die well in advance of changes of physical appearance on conventional images. We have recently discovered that PIT dramatically increases (20-fold) the delivery of nanoparticle sized therapies (e.g. liposomal chemotherapy) to PIT-treated cancer tissue. Therefore, the combination of PIT with nano-sized cancer reagents holds potential for even more effective therapy. Finally, we are now preparing clinical trials in head and neck and esophageal squamous cell cancer at NCI/Hopkins, National Cancer Center Singapore, and Netherland/Groningen Univ in collaboration with surgeons at these sites. We are working with the Image Probe Development Center (IPDC) to scale up production of antibody-IR700 conjugates for eventual use in these trials.

National Institute of Health (NIH)
National Cancer Institute (NCI)
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Nakajima, Kohei; Kimura, Toshihiro; Takakura, Hideo et al. (2018) Implantable wireless powered light emitting diode (LED) for near-infrared photoimmunotherapy: device development and experimental assessment in vitro and in vivo. Oncotarget 9:20048-20057
Maruoka, Yasuhiro; Nagaya, Tadanobu; Sato, Kazuhide et al. (2018) Near Infrared Photoimmunotherapy with Combined Exposure of External and Interstitial Light Sources. Mol Pharm 15:3634-3641
Nagaya, Tadanobu; Okuyama, Shuhei; Ogata, Fusa et al. (2018) Near infrared photoimmunotherapy targeting bladder cancer with a canine anti-epidermal growth factor receptor (EGFR) antibody. Oncotarget 9:19026-19038
Nagaya, Tadanobu; Gorka, Alexander P; Nani, Roger R et al. (2018) Molecularly Targeted Cancer Combination Therapy with Near-Infrared Photoimmunotherapy and Near-Infrared Photorelease with Duocarmycin-Antibody Conjugate. Mol Cancer Ther 17:661-670
Tang, Qinggong; Nagaya, Tadanobu; Liu, Yi et al. (2018) 3D mesoscopic fluorescence tomography for imaging micro-distribution of antibody-photon absorber conjugates during near infrared photoimmunotherapy in vivo. J Control Release 279:171-180
Okuyama, Shuhei; Nagaya, Tadanobu; Ogata, Fusa et al. (2017) Avoiding thermal injury during near-infrared photoimmunotherapy (NIR-PIT): the importance of NIR light power density. Oncotarget 8:113194-113201
Nagaya, Tadanobu; Nakamura, Yuko; Sato, Kazuhide et al. (2017) Near infrared photoimmunotherapy with avelumab, an anti-programmed death-ligand 1 (PD-L1) antibody. Oncotarget 8:8807-8817
Nagaya, Tadanobu; Nakamura, Yuko; Okuyama, Shuhei et al. (2017) Syngeneic Mouse Models of Oral Cancer Are Effectively Targeted by Anti-CD44-Based NIR-PIT. Mol Cancer Res 15:1667-1677
Tang, Qinggong; Nagaya, Tadanobu; Liu, Yi et al. (2017) Real-time monitoring of microdistribution of antibody-photon absorber conjugates during photoimmunotherapy in vivo. J Control Release 260:154-163
Ogata, Fusa; Nagaya, Tadanobu; Nakamura, Yuko et al. (2017) Near-infrared photoimmunotherapy: a comparison of light dosing schedules. Oncotarget 8:35069-35075

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