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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC011513-02
Application #
8938171
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
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
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
Nakamura, Yuko; Nagaya, Tadanobu; Sato, Kazuhide et al. (2017) Cerenkov Radiation-Induced Photoimmunotherapy with (18)F-FDG. J Nucl Med 58:1395-1400
Ito, Kimihiro; Mitsunaga, Makoto; Nishimura, Takashi et al. (2017) Near-Infrared Photochemoimmunotherapy by Photoactivatable Bifunctional Antibody-Drug Conjugates Targeting Human Epidermal Growth Factor Receptor 2 Positive Cancer. Bioconjug Chem 28:1458-1469
Ogawa, Mikako; Tomita, Yusuke; Nakamura, Yuko et al. (2017) Immunogenic cancer cell death selectively induced by near infrared photoimmunotherapy initiates host tumor immunity. Oncotarget 8:10425-10436
Nani, Roger R; Gorka, Alexander P; Nagaya, Tadanobu et al. (2017) In Vivo Activation of Duocarmycin-Antibody Conjugates by Near-Infrared Light. ACS Cent Sci 3:329-337
Nakamura, Yuko; Ohler, Zoe Weaver; Householder, Deborah et al. (2017) Near Infrared Photoimmunotherapy in a Transgenic Mouse Model of Spontaneous Epidermal Growth Factor Receptor (EGFR)-expressing Lung Cancer. Mol Cancer Ther 16:408-414

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