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
Open Access
- 28 June 2013
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 8 (6), e67904
- https://doi.org/10.1371/journal.pone.0067904
Abstract
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.Keywords
This publication has 41 references indexed in Scilit:
- The Tipping Point for Combination Therapy: Cancer Vaccines With Radiation, Chemotherapy, or Targeted Small Molecule InhibitorsSeminars in Oncology, 2012
- Myeloid-derived suppressor cells are implicated in regulating permissiveness for tumor metastasis during mouse gestationJCI Insight, 2011
- Chemotherapy Delivered After Viral Immunogene Therapy Augments Antitumor Efficacy Via Multiple Immune-mediated MechanismsMolecular Therapy, 2010
- Nanoparticle Delivery Systems in Cancer VaccinesPharmaceutical Research, 2010
- 5-Fluorouracil Selectively Kills Tumor-Associated Myeloid-Derived Suppressor Cells Resulting in Enhanced T Cell–Dependent Antitumor ImmunityCancer Research, 2010
- Adoptive transfer of HER2/neu-specific T cells expanded with alternating gamma chain cytokines mediate tumor regression when combined with the depletion of myeloid-derived suppressor cellsCancer Immunology, Immunotherapy, 2008
- Combination of Docetaxel and Recombinant Vaccine Enhances T-Cell Responses and Antitumor Activity: Effects of Docetaxel on Immune EnhancementClinical Cancer Research, 2008
- Immunosuppressive Strategies that are Mediated by Tumor CellsAnnual Review of Immunology, 2007
- Tumors induce a subset of inflammatory monocytes with immunosuppressive activity on CD8+ T cellsJCI Insight, 2006
- Molecular mechanisms of drug resistanceThe Journal of Pathology, 2005