title: Near infra-red photoimmunotherapy with anti-CEA-IR700 results in extensive tumor lysis and a significant decrease in tumor burden in orthotopic mouse models of pancreatic cancer.
abstract: Photoimmunotherapy (PIT) of cancer utilizes tumor-specific monoclonal antibodies conjugated to a photosensitizer phthalocyanine dye IR700 which becomes cytotoxic upon irradiation with near infrared light. In this study, we aimed to evaluate the efficacy of PIT on human pancreatic cancer cells in vitro and in vivo in an orthotopic nude mouse model. The binding capacity of anti-CEA antibody to BxPC-3 human pancreatic cancer cells was determined by FACS analysis. An in vitro cytotoxicity assay was used to determine cell death following treatment with PIT. For in vivo determination of PIT efficacy, nude mice were orthotopically implanted with BxPC-3 pancreatic tumors expressing green fluorescent protein (GFP). After tumor engraftment, the mice were divided into two groups: (1) treatment with anti-CEA-IR700 + 690 nm laser and (2) treatment with 690 nm laser only. Anti-CEA-IR700 (100 μg) was administered to group (1) via tail vein injection 24 hours prior to therapy. Tumors were then surgically exposed and treated with phototherapy at an intensity of 150 mW/cm2 for 30 minutes. Whole body imaging was done subsequently for 5 weeks using an OV-100 small animal imaging system. Anti-CEA-IR700 antibody bound to the BxPC3 cells to a high degree as shown by FACS analysis. Anti-CEA-IR700 caused extensive cancer cell killing after light activation compared to control cells in cytotoxicity assays. In the orthotopic models of pancreatic cancer, the anti-CEA-IR700 group had significantly smaller tumors than the control after 5 weeks (p<0.001). There was no significant difference in the body weights of mice in the anti-CEA-IR700 and control groups indicating that PIT was well tolerated by the mice.
authors: Department of Surgery, University of California San Diego, San Diego, California, United States of America.
authors: Ali A
authors: AA
authors: Maawy
authors: Department of Surgery, University of California San Diego, San Diego, California, United States of America; AntiCancer, Inc., San Diego, California, United States of America; Department of Surgery, Yokohama City University, Yokohama City, Japan.
authors: Yukihiko
authors: Y
authors: Hiroshima
authors: AntiCancer, Inc., San Diego, California, United States of America.
authors: Yong
authors: Y
authors: Zhang
authors: Aspyrian Therapeutics, San Diego, California, United States of America.
authors: Roger
authors: R
authors: Heim
authors: Aspyrian Therapeutics, San Diego, California, United States of America.
authors: Lew
authors: L
authors: Makings
authors: Aspyrian Therapeutics, San Diego, California, United States of America.
authors: Miguel
authors: M
authors: Garcia-Guzman
authors: OncoFluor, Inc., San Diego, California, United States of America.
authors: George A
authors: GA
authors: Luiken
authors: National Institutes of Health, Bethesda, Maryland, United States of America.
authors: Hisataka
authors: H
authors: Kobayashi
authors: Department of Surgery, University of California San Diego, San Diego, California, United States of America; AntiCancer, Inc., San Diego, California, United States of America.
authors: Robert M
authors: RM
authors: Hoffman
authors: Department of Surgery, University of California San Diego, San Diego, California, United States of America; Surgical Service, VA Healthcare System, San Diego, California, United States of America.
authors: Michael
authors: M
authors: Bouvet
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D045744:Cell Line, Tumor; D006801:Humans; D007167:Immunotherapy; D007259:Infrared Rays; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000628:therapy*; D010789:Phototherapy; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D011838:Radiation-Sensitizing Agents