Yukihiko Hiroshima1,2,3, Ali Maawy1, Yong Zhang2, Miguel Garcia Guzman4, Roger Heim4, Lew Makings4, George A Luiken5, Hisataka Kobayashi6, Kuniya Tanaka3, Itaru Endo3, Robert M Hoffman1,2, Michael Bouvet7,8. 1. Department of Surgery, Moores Cancer Center, University of California San Diego, San Diego, CA, USA. 2. AntiCancer, Inc., San Diego, CA, USA. 3. Yokohama City University Graduate School of Medicine, Yokohama, Japan. 4. Aspyrian Therapeutics, Inc., San Diego, CA, USA. 5. OncoFluor, Inc., San Diego, CA, USA. 6. National Institutes of Health, Bethesda, MD, USA. 7. Department of Surgery, Moores Cancer Center, University of California San Diego, San Diego, CA, USA. mbouvet@ucsd.edu. 8. VA San Diego Healthcare System, San Diego, CA, USA. mbouvet@ucsd.edu.
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). CONCLUSION: 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.
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). CONCLUSION: 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: Hannah M Hollandsworth; Thinzar M Lwin; Siamak Amirfakhri; Filemoni Filemoni; Surinder K Batra; Robert M Hoffman; Punita Dhawan; Michael Bouvet Journal: J Surg Res Date: 2019-05-09 Impact factor: 2.192
Authors: Elmire Hartmans; Matthijs D Linssen; Claire Sikkens; Afra Levens; Max J H Witjes; Gooitzen M van Dam; Wouter B Nagengast Journal: Oncotarget Date: 2017-05-02
Authors: Hannah M Hollandsworth; Siamak Amirfakhri; Filemoni Filemoni; Justin Molnar; Robert M Hoffman; Paul Yazaki; Michael Bouvet Journal: PLoS One Date: 2020-06-18 Impact factor: 3.240