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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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 |
format | Article |
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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.</description><identifier>ISSN: 0300-8177</identifier><identifier>EISSN: 1573-4919</identifier><identifier>DOI: 10.1007/s11010-015-2475-2</identifier><identifier>PMID: 26048718</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>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</subject><ispartof>Molecular and cellular biochemistry, 2015-09, Vol.407 (1-2), p.281-287</ispartof><rights>Springer Science+Business Media New York 2015</rights><rights>COPYRIGHT 2015 Springer</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c509t-6f29be0b3e63f69edc56b69b32ddeda584008e231fbc990bd801ccb1ce507733</citedby><cites>FETCH-LOGICAL-c509t-6f29be0b3e63f69edc56b69b32ddeda584008e231fbc990bd801ccb1ce507733</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11010-015-2475-2$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11010-015-2475-2$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26048718$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ingersoll, Susan B.</creatorcontrib><creatorcontrib>Ahmad, Sarfraz</creatorcontrib><creatorcontrib>McGann, Hasina C.</creatorcontrib><creatorcontrib>Banks, Robert K.</creatorcontrib><creatorcontrib>Stavitzski, Nicole M.</creatorcontrib><creatorcontrib>Srivastava, Milan</creatorcontrib><creatorcontrib>Ali, Ghazanfar</creatorcontrib><creatorcontrib>Finkler, Neil J.</creatorcontrib><creatorcontrib>Edwards, John R.</creatorcontrib><creatorcontrib>Holloway, Robert W.</creatorcontrib><title>Cellular therapy in combination with cytokines improves survival in a xenograft mouse model of ovarian cancer</title><title>Molecular and cellular biochemistry</title><addtitle>Mol Cell Biochem</addtitle><addtitle>Mol Cell Biochem</addtitle><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.</description><subject>Analysis</subject><subject>Animals</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Cancer patients</subject><subject>Cardiology</subject><subject>Cell Line, Tumor</subject><subject>Cellular biology</subject><subject>Combined Modality Therapy - methods</subject><subject>Cytokines</subject><subject>Drug Administration Schedule</subject><subject>Drug therapy</subject><subject>Female</subject><subject>Humans</subject><subject>Immunotherapy</subject><subject>Immunotherapy - methods</subject><subject>Injection</subject><subject>Interferon</subject><subject>Interferon-alpha - administration & dosage</subject><subject>Interferon-alpha - therapeutic use</subject><subject>Interleukin-2 - administration & dosage</subject><subject>Interleukin-2 - therapeutic use</subject><subject>Killer cells</subject><subject>Leukocytes, Mononuclear - transplantation</subject><subject>Life Sciences</subject><subject>Lymphocytes</subject><subject>Medical Biochemistry</subject><subject>Mice</subject><subject>Oncology</subject><subject>Ovarian cancer</subject><subject>Ovarian Neoplasms - immunology</subject><subject>Ovarian Neoplasms - therapy</subject><subject>Polyethylene Glycols - administration & dosage</subject><subject>Polyethylene Glycols - therapeutic use</subject><subject>Recombinant Proteins - administration & dosage</subject><subject>Recombinant Proteins - therapeutic use</subject><subject>Rodents</subject><subject>Survival</subject><subject>Survival Analysis</subject><subject>Treatment Outcome</subject><subject>Tumors</subject><subject>Xenograft Model Antitumor Assays</subject><issn>0300-8177</issn><issn>1573-4919</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kU9v1DAQxS0EokvhA3BBlrhwSRnbSRwfqxUUpEpcerdsZ7J1SezFTpbut8fRtvwTyNJ4ZP_m6Y0eIa8ZXDAA-T4zBgwqYE3Fa1nKE7JhjRRVrZh6SjYgAKqOSXlGXuR8BwUGxp6TM95C3UnWbci0xXFcRpPofIvJ7I_UB-riZH0ws4-BfvfzLXXHOX71ATP10z7FQ2nykg7-YMaVN_QeQ9wlM8x0ikvGUnscaRxoPJjkTZE0wWF6SZ4NZsz46uE-JzcfP9xsP1XXX64-by-vK9eAmqt24MoiWIGtGFqFvWta2yoreN9jb5quBuiQCzZYpxTYvgPmnGUOG5BSiHPy7iRbvH5bMM968tmVRU3AYk8zCbWoW6l4Qd_-hd7FJYVibqVEp3hTwy9qZ0bUPgxxTsatovqy5o1QHDpWqIt_UOX0OHkXAw6-vP8xwE4DLsWcEw56n_xk0lEz0GvC-pSwLgnrNWG9Gn7zYHixE_Y_Jx4jLQA_Abl8hR2m3zb6r-oPFtOweQ</recordid><startdate>20150901</startdate><enddate>20150901</enddate><creator>Ingersoll, Susan B.</creator><creator>Ahmad, Sarfraz</creator><creator>McGann, Hasina C.</creator><creator>Banks, Robert K.</creator><creator>Stavitzski, Nicole M.</creator><creator>Srivastava, Milan</creator><creator>Ali, Ghazanfar</creator><creator>Finkler, Neil J.</creator><creator>Edwards, John R.</creator><creator>Holloway, Robert W.</creator><general>Springer US</general><general>Springer</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7QP</scope><scope>7T5</scope><scope>7T7</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7N</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20150901</creationdate><title>Cellular therapy in combination with cytokines improves survival in a xenograft mouse model of ovarian cancer</title><author>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.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c509t-6f29be0b3e63f69edc56b69b32ddeda584008e231fbc990bd801ccb1ce507733</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Analysis</topic><topic>Animals</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Cancer patients</topic><topic>Cardiology</topic><topic>Cell Line, Tumor</topic><topic>Cellular biology</topic><topic>Combined Modality Therapy - methods</topic><topic>Cytokines</topic><topic>Drug Administration Schedule</topic><topic>Drug therapy</topic><topic>Female</topic><topic>Humans</topic><topic>Immunotherapy</topic><topic>Immunotherapy - methods</topic><topic>Injection</topic><topic>Interferon</topic><topic>Interferon-alpha - administration & dosage</topic><topic>Interferon-alpha - therapeutic use</topic><topic>Interleukin-2 - administration & dosage</topic><topic>Interleukin-2 - therapeutic use</topic><topic>Killer cells</topic><topic>Leukocytes, Mononuclear - transplantation</topic><topic>Life Sciences</topic><topic>Lymphocytes</topic><topic>Medical Biochemistry</topic><topic>Mice</topic><topic>Oncology</topic><topic>Ovarian cancer</topic><topic>Ovarian Neoplasms - immunology</topic><topic>Ovarian Neoplasms - therapy</topic><topic>Polyethylene Glycols - administration & dosage</topic><topic>Polyethylene Glycols - therapeutic use</topic><topic>Recombinant Proteins - administration & dosage</topic><topic>Recombinant Proteins - therapeutic use</topic><topic>Rodents</topic><topic>Survival</topic><topic>Survival Analysis</topic><topic>Treatment Outcome</topic><topic>Tumors</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ingersoll, Susan B.</creatorcontrib><creatorcontrib>Ahmad, Sarfraz</creatorcontrib><creatorcontrib>McGann, Hasina C.</creatorcontrib><creatorcontrib>Banks, Robert K.</creatorcontrib><creatorcontrib>Stavitzski, Nicole M.</creatorcontrib><creatorcontrib>Srivastava, Milan</creatorcontrib><creatorcontrib>Ali, Ghazanfar</creatorcontrib><creatorcontrib>Finkler, Neil J.</creatorcontrib><creatorcontrib>Edwards, John R.</creatorcontrib><creatorcontrib>Holloway, Robert W.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular and cellular biochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ingersoll, Susan B.</au><au>Ahmad, Sarfraz</au><au>McGann, Hasina C.</au><au>Banks, Robert K.</au><au>Stavitzski, Nicole M.</au><au>Srivastava, Milan</au><au>Ali, Ghazanfar</au><au>Finkler, Neil J.</au><au>Edwards, John R.</au><au>Holloway, Robert W.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cellular therapy in combination with cytokines improves survival in a xenograft mouse model of ovarian cancer</atitle><jtitle>Molecular and cellular biochemistry</jtitle><stitle>Mol Cell Biochem</stitle><addtitle>Mol Cell Biochem</addtitle><date>2015-09-01</date><risdate>2015</risdate><volume>407</volume><issue>1-2</issue><spage>281</spage><epage>287</epage><pages>281-287</pages><issn>0300-8177</issn><eissn>1573-4919</eissn><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-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.</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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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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