Photoimmunotherapy of gastric cancer peritoneal carcinomatosis in a mouse model

• Published in: PloS one Vol. 9; no. 11; p. e113276
• Main Authors: Sato, Kazuhide, Choyke, Peter L, Kobayashi, Hisataka
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 17-11-2014; Public Library of Science (PLoS)
• Subjects: Animals; Antibodies; Anticancer properties; Antigens; Antineoplastic Agents - therapeutic use; Apoptosis; Biocompatibility; Biology and Life Sciences; Biomarkers; Cancer; Cancer therapies; Cell Proliferation; Combined Modality Therapy; Cytotoxicity; ErbB-2 protein; Female; Flow Cytometry; Fluorescence; Fluorescent Antibody Technique; Gangrene; Gastric cancer; Green Fluorescent Proteins - metabolism; Humans; Immunoconjugates - therapeutic use; Immunoenzyme Techniques; Immunotherapy; Infrared radiation; Medical prognosis; Medical research; Medicine and Health Sciences; Metastasis; Mice; Mice, Nude; Microscopy; Microscopy, Fluorescence; Monoclonal antibodies; Pancreatic cancer; Peritoneal Neoplasms - immunology; Peritoneal Neoplasms - secondary; Peritoneal Neoplasms - therapy; Peritoneum; Photosensitizing Agents - therapeutic use; Phototherapy; Proteins; Spectrum analysis; Stomach cancer; Stomach Neoplasms - immunology; Stomach Neoplasms - pathology; Stomach Neoplasms - therapy; Targeted cancer therapy; Toxicity; Trastuzumab; Trastuzumab - therapeutic use; Tumor Burden; Tumor Cells, Cultured; Tumors; Xenograft Model Antitumor Assays; Xenografts; United States > US; Maryland
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0113276

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 of a photosensitizer, IR-700, conjugated to trastuzumab (tra-IR700), followed by NIR light was used for PIT. In vitro PIT was evaluated by measuring cytotoxicity with dead staining and a decrease in GFP fluorescence. In vivo PIT was evaluated in a disseminated peritoneal carcinomatosis model and a flank xenograft using tumor volume measurements and GFP fluorescence intensity. In vivo anti-tumor effects of PIT were confirmed by significant reductions in tumor volume (at day 15, p<0.0001 vs. control) and GFP fluorescence intensity (flank model: at day 3, PIT treated vs. control p<0.01 and peritoneal disseminated model: at day 3 PIT treated vs. control, p<0.05). Cytotoxic effects in vitro were shown to be dependent on the light dose and caused necrotic cell rupture leading to GFP release and a decrease in fluorescence intensity in vitro. Thus, loss of GFP fluorescence served as a useful biomarker of cell necrosis after PIT.