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
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