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

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...

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Veröffentlicht in:Molecular and cellular biochemistry 2015-09, Vol.407 (1-2), p.281-287
Hauptverfasser: Ingersoll, Susan B., Ahmad, Sarfraz, McGann, Hasina C., Banks, Robert K., Stavitzski, Nicole M., Srivastava, Milan, Ali, Ghazanfar, Finkler, Neil J., Edwards, John R., Holloway, Robert W.
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container_issue 1-2
container_start_page 281
container_title Molecular and cellular biochemistry
container_volume 407
creator Ingersoll, Susan B.
Ahmad, Sarfraz
McGann, Hasina C.
Banks, Robert K.
Stavitzski, Nicole M.
Srivastava, Milan
Ali, Ghazanfar
Finkler, Neil J.
Edwards, John R.
Holloway, Robert W.
description 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-IFN α -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-IFN α -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.
doi_str_mv 10.1007/s11010-015-2475-2
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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  &gt; 0.05). 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Therefore, in this study, we tested cellular immunotherapy and varying combinations of cytokines (IL-2 and/or pegylated-IFN α -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-IFN α -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  &gt; 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.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>26048718</pmid><doi>10.1007/s11010-015-2475-2</doi><tpages>7</tpages></addata></record>
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ispartof Molecular and cellular biochemistry, 2015-09, Vol.407 (1-2), p.281-287
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1573-4919
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source MEDLINE; SpringerLink Journals
subjects Analysis
Animals
Biochemistry
Biomedical and Life Sciences
Cancer patients
Cardiology
Cell Line, Tumor
Cellular biology
Combined Modality Therapy - methods
Cytokines
Drug Administration Schedule
Drug therapy
Female
Humans
Immunotherapy
Immunotherapy - methods
Injection
Interferon
Interferon-alpha - administration & dosage
Interferon-alpha - therapeutic use
Interleukin-2 - administration & dosage
Interleukin-2 - therapeutic use
Killer cells
Leukocytes, Mononuclear - transplantation
Life Sciences
Lymphocytes
Medical Biochemistry
Mice
Oncology
Ovarian cancer
Ovarian Neoplasms - immunology
Ovarian Neoplasms - therapy
Polyethylene Glycols - administration & dosage
Polyethylene Glycols - therapeutic use
Recombinant Proteins - administration & dosage
Recombinant Proteins - therapeutic use
Rodents
Survival
Survival Analysis
Treatment Outcome
Tumors
Xenograft Model Antitumor Assays
title Cellular therapy in combination with cytokines improves survival in a xenograft mouse model of ovarian cancer
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