The combination of a low-dose chemotherapeutic agent, 5-fluorouracil, and an adenoviral tumor vaccine has a synergistic benefit on survival in a tumor model system
Standard cancer therapies, particularly those involving chemotherapy, are in need of modifications that both reduce short-term and long-term side effects as well as improve the overall survival of cancer patients. Here we show that combining low-dose chemotherapy with a therapeutic vaccination using...
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| Veröffentlicht in: | PloS one 2013-06, Vol.8 (6), p.e67904 |
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| creator | Geary, Sean M Lemke, Caitlin D Lubaroff, David M Salem, Aliasger K |
| description | Standard cancer therapies, particularly those involving chemotherapy, are in need of modifications that both reduce short-term and long-term side effects as well as improve the overall survival of cancer patients. Here we show that combining low-dose chemotherapy with a therapeutic vaccination using an adenovirus encoding a model tumor-associated antigen, ovalbumin (Ad5-OVA), had a synergistic impact on survival in tumor-challenged mice. Mice that received the combinatorial treatment of Ad5-OVA plus low-dose 5-fluorouracil (5-FU) had a 95% survival rate compared to 7% and 30% survival rates for Ad5-OVA alone and 5-FU alone respectively. The presence of 5-FU enhanced the levels of OVA-specific CD8(+) T lymphocytes in the spleens and draining lymph nodes of Ad5-OVA-treated mice, a phenomenon that was dependent on the mice having been tumor-challenged. Thus 5-FU may have enhanced survival of Ad5-OVA-treated mice by enhancing the tumor-specific immune response combined with eliminating tumor bulk. We also investigated the possibility that the observed therapeutic benefit may have been derived from the capacity of 5-FU to deplete MDSC populations. The findings presented here promote the concept of combining adenoviral cancer vaccines with low-dose chemotherapy. |
| doi_str_mv | 10.1371/journal.pone.0067904 |
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The findings presented here promote the concept of combining adenoviral cancer vaccines with low-dose chemotherapy.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0067904</identifier><identifier>PMID: 23840786</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>5-Fluorouracil ; Adenoviridae - immunology ; Adenoviruses ; Animals ; Antigen (tumor-associated) ; Antigens ; Antigens, Neoplasm - immunology ; Antineoplastic Agents - administration & dosage ; Antineoplastic Agents - immunology ; Antineoplastic Combined Chemotherapy Protocols - administration & dosage ; Antineoplastic Combined Chemotherapy Protocols - immunology ; Biology ; Cancer ; Cancer therapies ; Cancer vaccines ; Cancer Vaccines - administration & dosage ; Cancer Vaccines - immunology ; CD8 antigen ; CD8-Positive T-Lymphocytes - drug effects ; CD8-Positive T-Lymphocytes - immunology ; Chemotherapy ; Clinical trials ; Combinatorial analysis ; Dendritic cells ; Dosage ; Drug dosages ; Drug Synergism ; Fluorouracil - administration & dosage ; Fluorouracil - immunology ; Granulocytes ; Immune response ; Immune system ; Immunotherapy ; Lymph nodes ; Lymph Nodes - drug effects ; Lymph Nodes - immunology ; Lymphatic system ; Lymphocytes ; Lymphocytes T ; Male ; Medicine ; Mice ; Mice, Inbred C57BL ; Ovalbumin ; Ovalbumin - administration & dosage ; Ovalbumin - immunology ; Pharmaceutical sciences ; Pharmacy ; Rodents ; Side effects ; Spleen - drug effects ; Spleen - immunology ; Studies ; Survival ; Survival Rate ; Tumors ; Vaccines</subject><ispartof>PloS one, 2013-06, Vol.8 (6), p.e67904</ispartof><rights>2013 Geary et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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Here we show that combining low-dose chemotherapy with a therapeutic vaccination using an adenovirus encoding a model tumor-associated antigen, ovalbumin (Ad5-OVA), had a synergistic impact on survival in tumor-challenged mice. Mice that received the combinatorial treatment of Ad5-OVA plus low-dose 5-fluorouracil (5-FU) had a 95% survival rate compared to 7% and 30% survival rates for Ad5-OVA alone and 5-FU alone respectively. The presence of 5-FU enhanced the levels of OVA-specific CD8(+) T lymphocytes in the spleens and draining lymph nodes of Ad5-OVA-treated mice, a phenomenon that was dependent on the mice having been tumor-challenged. Thus 5-FU may have enhanced survival of Ad5-OVA-treated mice by enhancing the tumor-specific immune response combined with eliminating tumor bulk. We also investigated the possibility that the observed therapeutic benefit may have been derived from the capacity of 5-FU to deplete MDSC populations. The findings presented here promote the concept of combining adenoviral cancer vaccines with low-dose chemotherapy.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23840786</pmid><doi>10.1371/journal.pone.0067904</doi><oa>free_for_read</oa></addata></record> |
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| subjects | 5-Fluorouracil Adenoviridae - immunology Adenoviruses Animals Antigen (tumor-associated) Antigens Antigens, Neoplasm - immunology Antineoplastic Agents - administration & dosage Antineoplastic Agents - immunology Antineoplastic Combined Chemotherapy Protocols - administration & dosage Antineoplastic Combined Chemotherapy Protocols - immunology Biology Cancer Cancer therapies Cancer vaccines Cancer Vaccines - administration & dosage Cancer Vaccines - immunology CD8 antigen CD8-Positive T-Lymphocytes - drug effects CD8-Positive T-Lymphocytes - immunology Chemotherapy Clinical trials Combinatorial analysis Dendritic cells Dosage Drug dosages Drug Synergism Fluorouracil - administration & dosage Fluorouracil - immunology Granulocytes Immune response Immune system Immunotherapy Lymph nodes Lymph Nodes - drug effects Lymph Nodes - immunology Lymphatic system Lymphocytes Lymphocytes T Male Medicine Mice Mice, Inbred C57BL Ovalbumin Ovalbumin - administration & dosage Ovalbumin - immunology Pharmaceutical sciences Pharmacy Rodents Side effects Spleen - drug effects Spleen - immunology Studies Survival Survival Rate Tumors Vaccines |
| title | The combination of a low-dose chemotherapeutic agent, 5-fluorouracil, and an adenoviral tumor vaccine has a synergistic benefit on survival in a tumor model system |
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