title: Cellular therapy in combination with cytokines improves survival in a xenograft mouse model of ovarian cancer.
abstract: 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 × 10(6) 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 (7.3 weeks) compared to mice with no treatment (4.2 weeks), IL-2 (3.5 weeks), PBMC (4.0 weeks), or PBMC plus IL-2 and IFN (4.3 weeks), although PBMC plus IL-2 was not statistically different than PBMC plus IFN (5.5 weeks, 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.
authors.affiliation: Florida Hospital Gynecologic Oncology, Florida Hospital Cancer Institute, 2501 N. Orange Ave., Suite 786, Orlando, FL, 32804, USA, singersoll@valenciacollege.edu.
authors.forename: Susan B
authors.initials: SB
authors.lastname: Ingersoll
authors.forename: Sarfraz
authors.initials: S
authors.lastname: Ahmad
authors.forename: Hasina C
authors.initials: HC
authors.lastname: McGann
authors.forename: Robert K
authors.initials: RK
authors.lastname: Banks
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Stavitzski
authors.forename: Milan
authors.initials: M
authors.lastname: Srivastava
authors.forename: Ghazanfar
authors.initials: G
authors.lastname: Ali
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Finkler
authors.forename: John R
authors.initials: JR
authors.lastname: Edwards
authors.forename: Robert W
authors.initials: RW
authors.lastname: Holloway
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy / Q000379:methods*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000627:therapeutic use; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000627:therapeutic use; D007963:Leukocytes, Mononuclear / Q000637:transplantation*; D051379:Mice; D010051:Ovarian Neoplasms / Q000276:immunology / Q000628:therapy*; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D016019:Survival Analysis; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007376:Interleukin-2; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C417083:peginterferon alfa-2b