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
Sato, Kazuhide; Watanabe, Rira; Hanaoka, Hirofumi et al. (2014) Photoimmunotherapy: comparative effectiveness of two monoclonal antibodies targeting the epidermal growth factor receptor. Mol Oncol 8:620-32
Sano, Kohei; Nakajima, Takahito; Choyke, Peter L et al. (2014) The effect of photoimmunotherapy followed by liposomal daunorubicin in a mixed tumor model: a demonstration of the super-enhanced permeability and retention effect after photoimmunotherapy. Mol Cancer Ther 13:426-32
Ali, Towhid; Nakajima, Takahito; Sano, Kohei et al. (2014) Dynamic fluorescent imaging with indocyanine green for monitoring the therapeutic effects of photoimmunotherapy. Contrast Media Mol Imaging 9:276-82
Sano, Kohei; Mitsunaga, Makoto; Nakajima, Takahito et al. (2013) Acute cytotoxic effects of photoimmunotherapy assessed by 18F-FDG PET. J Nucl Med 54:770-5
Sano, Kohei; Nakajima, Takahito; Choyke, Peter L et al. (2013) Markedly enhanced permeability and retention effects induced by photo-immunotherapy of tumors. ACS Nano 7:717-24