Near-infrared photoimmunotherapy with galactosyl serum albumin in a model of diffuse peritoneal disseminated ovarian cancer
Autor: | Peter L. Choyke, Shuhei Okuyama, Yuko Nakamura, Kazuhide Sato, Hisataka Kobayashi, Fusa Ogata, Tadanobu Nagaya, Toshiko Harada |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Immunoconjugates Cell Survival Infrared Rays near-infrared photoimmunotherapy Serum albumin Mice 03 medical and health sciences 0302 clinical medicine In vivo Albumins Cell Line Tumor medicine Animals Humans neoplasms Peritoneal Neoplasms Cell Proliferation Ovarian Neoplasms galactosyl serum albumin Photosensitizing Agents biology Chemistry technology industry and agriculture Albumin Galactose Cancer Photoimmunotherapy Phototherapy equipment and supplies medicine.disease Xenograft Model Antitumor Assays 3. Good health surgical procedures operative ovarian cancer 030104 developmental biology Cell killing Oncology Biochemistry 030220 oncology & carcinogenesis beta-D-galactose receptor biology.protein Cancer research Female Immunotherapy Antibody Ovarian cancer peritoneal cancer metastases Research Paper |
Zdroj: | Oncotarget |
ISSN: | 1949-2553 |
Popis: | // Toshiko Harada 1 , Yuko Nakamura 1 , Kazuhide Sato 1 , Tadanobu Nagaya 1 , Shuhei Okuyama 1 , Fusa Ogata 1 , Peter L. Choyke 1 , Hisataka Kobayashi 1 1 Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, 20892, USA Correspondence to: Hisataka Kobayashi, email: kobayash@mail.nih.gov Keywords: near-infrared photoimmunotherapy, ovarian cancer, peritoneal cancer metastases, galactosyl serum albumin, beta-D-galactose receptor Received: August 15, 2016 Accepted: September 30, 2016 Published: October 17, 2016 ABSTRACT Near-infrared photoimmunotherapy (NIR-PIT) is a highly cell-selective cancer therapy based on an armed antibody conjugated with a phthalocyanine-based photo-absorber, IRDye700DX (IR700). NIR-PIT can quickly kill target cells that express specific proteins on the cellular membrane but only when the antibody-IR700 conjugate binds to the cell membrane and is then exposed to NIR light. NIR-PIT is highly selective based on the specificity of the antibody. Galactosyl serum albumin (GSA) is composed of albumin decorated with galactose molecules conjugated to the carboxyl groups of albumin. GSA binds to beta-D-galactose receptors, a surface lectin, which are overexpressed on the cell surface of many cancers, including ovarian cancers and is quickly internalized after binding. Here, we demonstrate the feasibility of NIR-PIT in a model of disseminated peritoneal ovarian cancer (SHIN3 cells) using GSA-IR700 that binds to beta-D-galactose receptors. GSA-IR700 bound quickly to SHIN3 cells, then accumulated in the endo-lysosomes. Cell-specific killing was observed in vitro , yet a relatively large dose of NIR light exposure was required for cell killing compared to antibody-IR700 conjugates. To evaluate in vivo therapeutic effects of GSA-IR700 NIR-PIT, peritoneal disseminated SHIN3 tumor-bearing mice were separated into four groups: no treatment; NIR light only; GSA-IR700 only; and GSA-IR700 NIR-PIT. Repeated NIR-PIT showed significant suppression of tumor based on bioluminescence compared to the other groups (p < 0.05). Thus, repeated NIR-PIT using GSA-IR700 can achieve efficient antitumor effects, although GSA-IR700 NIR-PIT was less effective than antibody-IR700 NIR-PIT conjugates likely due to the rapid internalization of GSA-IR700. |
Databáze: | OpenAIRE |
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