Molecular targeted photoimmunotherapy for HER2-positive human gastric cancer in combination with chemotherapy results in improved treatment outcomes through different cytotoxic mechanisms

Published on Jan 25, 2016in BMC Cancer3.15
· DOI :10.1186/S12885-016-2072-0
Kimihiro Ito5
Estimated H-index: 5
(Jikei University School of Medicine),
Makoto Mitsunaga15
Estimated H-index: 15
(Jikei University School of Medicine)
+ 4 AuthorsHisao Tajiri63
Estimated H-index: 63
(Jikei University School of Medicine)
Sources
Abstract
Background Photoimmunotherapy (PIT) is a novel type of molecular optical imaging-guided cancer phototherapy based on a monoclonal antibody conjugated to a photosensitizer, IR700, in combination with near-infrared (NIR) light. PIT rapidly causes target-specific cell death by inducing cell membrane damages and appears to be highly effective; however, we have previously demonstrated that tumor recurrences were eventually seen in PIT-treated mice, likely owing to inhomogeneous mAb-IR700 conjugate distribution in the tumor, thus limiting the effectiveness of PIT as a monotherapy. Here, we examined the effects of human epidermal growth factor-2 (HER2)-targeted PIT in combination with 5-fluorouracil (5-FU) compared to PIT alone for HER2-expressing human gastric cancer cells.
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Photoimmunotherapy (PIT) is a new cancer treatment that combines the specificity of antibodies for targeting tumors with the toxicity induced by photosensitizers after exposure to near infrared (NIR) light. We performed PIT in a model of disseminated gastric cancer peritoneal carcinomatosis and monitored efficacy with in vivo GFP fluorescence imaging. In vitro and in vivo experiments were conducted with a HER2-expressing, GFP-expressing, gastric cancer cell line (N87-GFP). A conjugate comprised ...
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Armed antibody-based targeted molecular therapies offer the possibility of effective tumor control with a minimum of side effects. Photoimmunotherapy (PIT) employs a monoclonal antibody–phototoxic phthalocyanine dye, IR700 conjugate, that is activated by focal near-infrared (NIR) light irradiation after antibody binding to the targeted tumor cell surface leading to rapid necrotic cell death. Therapy by single NIR light irradiation was effective without significant side effects; however, recurren...
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Makoto Mitsunaga et al. have developed a new form of molecular-targeted cancer therapy that provides an alternative to current photodynamic approaches where damage to surrounding healthy cells and tissues can be a problem. They use a target-specific photosensitizer based on a near-infrared phthalocyanine dye, which is conjugated to monoclonal antibodies targeting human epidermal growth factor receptors (HER1 and HER2). Selective treatment using this approach was shown in vivo in subcutaneous can...
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