caa a22 4500 60623568X CHVBK 20210128101243.0 cr unu---uuuuu 210128e20150901xx s 000 0 eng 10.1007/s11010-015-2475-2 doi (NATIONALLICENCE)springer-10.1007/s11010-015-2475-2 Cellular therapy in combination with cytokines improves survival in a xenograft mouse model of ovarian cancer [Elektronische Daten] [Susan Ingersoll, Sarfraz Ahmad, Hasina McGann, Robert Banks, Nicole Stavitzski, Milan Srivastava, Ghazanfar Ali, Neil Finkler, John Edwards, Robert Holloway] Studies have shown enhanced survival of ovarian cancer patients in which the tumors are infiltrated with tumor infiltrating lymphocytes and natural killer cells showing the importance of immune surveillance and recognition in ovarian cancer. Therefore, in this study, we tested cellular immunotherapy and varying combinations of cytokines (IL-2 and/or pegylated-IFNα-2b) in a xenograft mouse model of ovarian cancer. SKOV3-AF2 ovarian cancer cells were injected intra-peritoneally (IP) into athymic nude mice. On day 7 post-tumor cell injection, mice were injected IP with peripheral blood mononuclear cells (PBMC; 5×106 PBMC) and cytokine combinations [IL-2±pegylated-IFNα-2b (IFN)]. Cytokine injections were continued weekly for IFN (12,000 U/injection) and thrice weekly for IL-2 (4000 U/injection). Mice were euthanized when they became moribund due to tumor burden at which time tumor and ascitic fluid were measured and collected. Treatment efficacy was measured by improved survival at 8 weeks and overall survival by Kaplan-Meier analysis. We observed that the mice tolerated all treatment combinations without significant weight loss or other apparent illness. Mice receiving PBMC plus IL-2 showed improved median survival (7.3weeks) compared to mice with no treatment (4.2weeks), IL-2 (3.5weeks), PBMC (4.0weeks), or PBMC plus IL-2 and IFN (4.3weeks), although PBMC plus IL-2 was not statistically different than PBMC plus IFN (5.5weeks, p>0.05). We demonstrate that cytokine-stimulated cellular immune therapy with PBMC and IL-2 was well tolerated and resulted in survival advantage compared to untreated controls and other cytokine combinations in the nude-mouse model. Springer Science+Business Media New York, 2015 Cellular therapy nationallicence Cytokines nationallicence Ovarian cancer nationallicence Xenograft mouse model nationallicence Peripheral blood mononuclear cells nationallicence Ingersoll Susan Florida Hospital Gynecologic Oncology, Florida Hospital Cancer Institute, 2501 N. Orange Ave., Suite 786, 32804, Orlando, FL, USA aut Ahmad Sarfraz Florida Hospital Gynecologic Oncology, Florida Hospital Cancer Institute, 2501 N. Orange Ave., Suite 786, 32804, Orlando, FL, USA aut McGann Hasina Florida Hospital Gynecologic Oncology, Florida Hospital Cancer Institute, 2501 N. Orange Ave., Suite 786, 32804, Orlando, FL, USA aut Banks Robert University of Central Florida College of Medicine, 32827, Orlando, FL, USA aut Stavitzski Nicole Florida Hospital Gynecologic Oncology, Florida Hospital Cancer Institute, 2501 N. Orange Ave., Suite 786, 32804, Orlando, FL, USA aut Srivastava Milan Florida Hospital Gynecologic Oncology, Florida Hospital Cancer Institute, 2501 N. Orange Ave., Suite 786, 32804, Orlando, FL, USA aut Ali Ghazanfar Florida Hospital Gynecologic Oncology, Florida Hospital Cancer Institute, 2501 N. Orange Ave., Suite 786, 32804, Orlando, FL, USA aut Finkler Neil Florida Hospital Gynecologic Oncology, Florida Hospital Cancer Institute, 2501 N. Orange Ave., Suite 786, 32804, Orlando, FL, USA aut Edwards John University of Central Florida College of Medicine, 32827, Orlando, FL, USA aut Holloway Robert Florida Hospital Gynecologic Oncology, Florida Hospital Cancer Institute, 2501 N. Orange Ave., Suite 786, 32804, Orlando, FL, USA aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 407/1-2(2015-09-01), 281-287 0300-8177 407:1-2<281 2015 407 11010 https://doi.org/10.1007/s11010-015-2475-2 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2475-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Ingersoll Susan Florida Hospital Gynecologic Oncology, Florida Hospital Cancer Institute, 2501 N. Orange Ave., Suite 786, 32804, Orlando, FL, USA aut NATIONALLICENCE 700 1- Ahmad Sarfraz Florida Hospital Gynecologic Oncology, Florida Hospital Cancer Institute, 2501 N. Orange Ave., Suite 786, 32804, Orlando, FL, USA aut NATIONALLICENCE 700 1- McGann Hasina Florida Hospital Gynecologic Oncology, Florida Hospital Cancer Institute, 2501 N. Orange Ave., Suite 786, 32804, Orlando, FL, USA aut NATIONALLICENCE 700 1- Banks Robert University of Central Florida College of Medicine, 32827, Orlando, FL, USA aut NATIONALLICENCE 700 1- Stavitzski Nicole Florida Hospital Gynecologic Oncology, Florida Hospital Cancer Institute, 2501 N. Orange Ave., Suite 786, 32804, Orlando, FL, USA aut NATIONALLICENCE 700 1- Srivastava Milan Florida Hospital Gynecologic Oncology, Florida Hospital Cancer Institute, 2501 N. Orange Ave., Suite 786, 32804, Orlando, FL, USA aut NATIONALLICENCE 700 1- Ali Ghazanfar Florida Hospital Gynecologic Oncology, Florida Hospital Cancer Institute, 2501 N. Orange Ave., Suite 786, 32804, Orlando, FL, USA aut NATIONALLICENCE 700 1- Finkler Neil Florida Hospital Gynecologic Oncology, Florida Hospital Cancer Institute, 2501 N. Orange Ave., Suite 786, 32804, Orlando, FL, USA aut NATIONALLICENCE 700 1- Edwards John University of Central Florida College of Medicine, 32827, Orlando, FL, USA aut NATIONALLICENCE 700 1- Holloway Robert Florida Hospital Gynecologic Oncology, Florida Hospital Cancer Institute, 2501 N. Orange Ave., Suite 786, 32804, Orlando, FL, USA aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 407/1-2(2015-09-01), 281-287 0300-8177 407:1-2<281 2015 407 11010