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 #
1ZIABC011513-01
Application #
8763579
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2013
Total Cost
$337,559
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Ishida, Michihiro; Kagawa, Shunsuke; Shimoyama, Kyoko et al. (2016) Trastuzumab-Based Photoimmunotherapy Integrated with Viral HER2 Transduction Inhibits Peritoneally Disseminated HER2-Negative Cancer. Mol Cancer Ther 15:402-11
Jin, Jiefu; Krishnamachary, Balaji; Mironchik, Yelena et al. (2016) Phototheranostics of CD44-positive cell populations in triple negative breast cancer. Sci Rep 6:27871
Nagaya, Tadanobu; Nakamura, Yuko; Sato, Kazuhide et al. (2016) Near infrared photoimmunotherapy with an anti-mesothelin antibody. Oncotarget 7:23361-9
Kobayashi, Hisataka; Choyke, Peter L (2016) Super enhanced permeability and retention (SUPR) effects in tumors following near infrared photoimmunotherapy. Nanoscale 8:12504-9
Ito, Kimihiro; Mitsunaga, Makoto; Nishimura, Takashi et al. (2016) Combination photoimmunotherapy with monoclonal antibodies recognizing different epitopes of human epidermal growth factor receptor 2: an assessment of phototherapeutic effect based on fluorescence molecular imaging. Oncotarget 7:14143-52
Ito, Kimihiro; Mitsunaga, Makoto; Arihiro, Seiji et al. (2016) Molecular targeted photoimmunotherapy for HER2-positive human gastric cancer in combination with chemotherapy results in improved treatment outcomes through different cytotoxic mechanisms. BMC Cancer 16:37
Nagaya, Tadanobu; Nakamura, Yuko; Sato, Kazuhide et al. (2016) Near infrared photoimmunotherapy of B-cell lymphoma. Mol Oncol 10:1404-1414
Jing, Hua; Weidensteiner, Claudia; Reichardt, Wilfried et al. (2016) Imaging and Selective Elimination of Glioblastoma Stem Cells with Theranostic Near-Infrared-Labeled CD133-Specific Antibodies. Theranostics 6:862-74
Sato, Kazuhide; Watanabe, Rira; Hanaoka, Hirofumi et al. (2016) Comparative effectiveness of light emitting diodes (LEDs) and Lasers in near infrared photoimmunotherapy. Oncotarget 7:14324-35
Nagaya, Tadanobu; Nakamura, Yuko; Sato, Kazuhide et al. (2016) Improved micro-distribution of antibody-photon absorber conjugates after initial near infrared photoimmunotherapy (NIR-PIT). J Control Release 232:1-8

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