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

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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.

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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.

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Authors and Affiliations

  1. Florida Hospital Gynecologic Oncology, Florida Hospital Cancer Institute, 2501 N. Orange Ave., Suite 786, Orlando, FL, 32804, USA

    Susan B. Ingersoll, Sarfraz Ahmad, Hasina C. McGann, Nicole M. Stavitzski, Milan Srivastava, Ghazanfar Ali, Neil J. Finkler & Robert W. Holloway

  2. Florida State University College of Medicine, Orlando, FL, 32801, USA

    Susan B. Ingersoll, Sarfraz Ahmad, Neil J. Finkler & Robert W. Holloway

  3. University of Central Florida College of Medicine, Orlando, FL, 32827, USA

    Sarfraz Ahmad, Robert K. Banks, Neil J. Finkler, John R. Edwards & Robert W. Holloway

  4. Indiana Blood and Marrow Transplantation, Indianapolis, IN, 46237, USA

    John R. Edwards

Authors
  1. Susan B. Ingersoll
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  2. Sarfraz Ahmad
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  3. Hasina C. McGann
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  4. Robert K. Banks
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  5. Nicole M. Stavitzski
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  6. Milan Srivastava
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  7. Ghazanfar Ali
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  8. Neil J. Finkler
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  9. John R. Edwards
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  10. Robert W. Holloway
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Corresponding authors

Correspondence to Susan B. Ingersoll or Sarfraz Ahmad.

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Ingersoll, S.B., Ahmad, S., McGann, H.C. et al. Cellular therapy in combination with cytokines improves survival in a xenograft mouse model of ovarian cancer. Mol Cell Biochem 407, 281–287 (2015). https://doi.org/10.1007/s11010-015-2475-2

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  • DOI: https://doi.org/10.1007/s11010-015-2475-2

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