title: Photoimmunotherapy Inhibits Tumor Recurrence After Surgical Resection on a Pancreatic Cancer Patient-Derived Orthotopic Xenograft (PDOX) Nude Mouse Model.
abstract: BACKGROUND
  Photoimmunotherapy (PIT) uses a target-specific photosensitizer based on a near-infrared (NIR) phthalocyanine dye, IR700, to induce tumor necrosis after irradiation with NIR light to kill cancer cells, such as those that remain after surgery. The purpose of the present study was to sterilize the surgical bed after pancreatic cancer resection with PIT in carcinoembryonic antigen (CEA)-expressing, patient-derived, orthotopic xenograft (PDOX) nude mouse models.
  
  
  METHODS
  After confirmation of tumor engraftment, mice were randomized to two groups: bright light surgery (BLS)-only and BLS + PIT. Each treatment arm consisted of seven tumor-bearing mice. BLS was performed under standard bright-field with an MVX10 long-working distance, high-magnification microscope on all mice. For BLS + PIT, anti-CEA antibody conjugated with IR700 (anti-CEA-IR700) (50 µg) was injected intravenously in all mice 24 h before surgery. After the surgery, the resection bed was then irradiated with a red-light-emitting diode at 690 ± 5 nm with a power density of 150 mW/cm(2).
  
  
  RESULTS
  Anti-CEA-IR700 labelled and illuminated the pancreatic cancer PDOX. Minimal residual cancer of the PDOX was detected by fluorescence after BLS. The local recurrence rate was 85.7 % for BLS-only and 28.6 % for BLS + PIT-treated mice (p = 0.05). The average recurrent tumor weight was 1149.0 ± 794.6 mg for BLS-only and 210.8 ± 336.9 mg for BLS + PIT-treated mice (p = 0.015).
  
  
  CONCLUSIONS
  Anti-CEA-IR700 was able to label and illuminate a pancreatic cancer PDOX nude mouse model sufficiently for PIT. PIT reduced recurrence by eliminating remaining residual cancer cells after BLS.
authors.affiliation: Department of Surgery, Moores Cancer Center, University of California San Diego, San Diego, CA, USA.|AntiCancer, Inc., San Diego, CA, USA.|Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Hiroshima
authors.affiliation: Department of Surgery, Moores Cancer Center, University of California San Diego, San Diego, CA, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Maawy
authors.affiliation: AntiCancer, Inc., San Diego, CA, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Aspyrian Therapeutics, Inc., San Diego, CA, USA.
authors.forename: Miguel Garcia
authors.initials: MG
authors.lastname: Guzman
authors.affiliation: Aspyrian Therapeutics, Inc., San Diego, CA, USA.
authors.forename: Roger
authors.initials: R
authors.lastname: Heim
authors.affiliation: Aspyrian Therapeutics, Inc., San Diego, CA, USA.
authors.forename: Lew
authors.initials: L
authors.lastname: Makings
authors.affiliation: OncoFluor, Inc., San Diego, CA, USA.
authors.forename: George A
authors.initials: GA
authors.lastname: Luiken
authors.affiliation: National Institutes of Health, Bethesda, MD, USA.
authors.forename: Hisataka
authors.initials: H
authors.lastname: Kobayashi
authors.affiliation: Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Kuniya
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Itaru
authors.initials: I
authors.lastname: Endo
authors.affiliation: Department of Surgery, Moores Cancer Center, University of California San Diego, San Diego, CA, USA.|AntiCancer, Inc., San Diego, CA, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoffman
authors.affiliation: Department of Surgery, Moores Cancer Center, University of California San Diego, San Diego, CA, USA. mbouvet@ucsd.edu.|VA San Diego Healthcare System, San Diego, CA, USA. mbouvet@ucsd.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Bouvet
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D006801:Humans; D007124:Immunoenzyme Techniques; D007167:Immunotherapy; D051379:Mice; D008819:Mice, Nude; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000276:immunology / Q000601:surgery; D018365:Neoplasm, Residual / Q000188:drug therapy / Q000276:immunology / Q000601:surgery; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000601:surgery; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D017319:Photosensitizing Agents