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
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
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
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
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
Ogata, Fusa; Nagaya, Tadanobu; Nakamura, Yuko et al. (2017) Near-infrared photoimmunotherapy: a comparison of light dosing schedules. Oncotarget 8:35069-35075
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
Nagaya, Tadanobu; Nakamura, Yuko; Okuyama, Shuhei et al. (2017) Near-Infrared Photoimmunotherapy Targeting Prostate Cancer with Prostate-Specific Membrane Antigen (PSMA) Antibody. Mol Cancer Res 15:1153-1162

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