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Molecular and Cellular Biochemistry

, Volume 407, Issue 1–2, pp 281–287 | Cite as

Cellular therapy in combination with cytokines improves survival in a xenograft mouse model of ovarian cancer

  • Susan B. Ingersoll
  • Sarfraz Ahmad
  • Hasina C. McGann
  • Robert K. Banks
  • Nicole M. Stavitzski
  • Milan Srivastava
  • Ghazanfar Ali
  • Neil J. Finkler
  • John R. Edwards
  • Robert W. Holloway
Article

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 × 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 (7.3 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.

Keywords

Cellular therapy Cytokines Ovarian cancer Xenograft mouse model Peripheral blood mononuclear cells 

Notes

Acknowledgments

The authors would like to thank Mr. Brian Kirk for his technical help with a portion of the animal experiments. This research study was funded by the Bankhead-Coley Cancer Research Program (State of Florida Department of Health) and partial support from the Ovarian Cancer Alliance of Florida, the Gala Endowed Program for Oncologic Research, and the Wonderful Whacky Women of Florida, Redneck Riviera Chapter.

Conflict of interest

None.

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Susan B. Ingersoll
    • 1
    • 2
  • Sarfraz Ahmad
    • 1
    • 2
    • 3
  • Hasina C. McGann
    • 1
  • Robert K. Banks
    • 3
  • Nicole M. Stavitzski
    • 1
  • Milan Srivastava
    • 1
  • Ghazanfar Ali
    • 1
  • Neil J. Finkler
    • 1
    • 2
    • 3
  • John R. Edwards
    • 3
    • 4
  • Robert W. Holloway
    • 1
    • 2
    • 3
  1. 1.Florida Hospital Gynecologic OncologyFlorida Hospital Cancer InstituteOrlandoUSA
  2. 2.Florida State University College of MedicineOrlandoUSA
  3. 3.University of Central Florida College of MedicineOrlandoUSA
  4. 4.Indiana Blood and Marrow TransplantationIndianapolisUSA

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