Photoimmunotherapy of gastric cancer peritoneal carcinomatosis in a mouse model.
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.
Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, United States of America.
Kazuhide
K
Sato
Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, United States of America.
Peter L
PL
Choyke
Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, United States of America.
Hisataka
H
Kobayashi
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis; D049109:Cell Proliferation; D003131:Combined Modality Therapy; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use*; D007124:Immunoenzyme Techniques; D007167:Immunotherapy; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D010534:Peritoneal Neoplasms / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D010789:Phototherapy; D013274:Stomach Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D000068878:Trastuzumab / Q000627:therapeutic use*; D047368:Tumor Burden; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D018796:Immunoconjugates; D017319:Photosensitizing Agents; D049452:Green Fluorescent Proteins; D000068878:Trastuzumab