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Antitumor effects of anti-CD40/CpG immunotherapy combined with gemcitabine or 5- fluorouracil chemotherapy in the B16 melanoma model

  • Alexander Rakhmilevich
  • Xiaoyi Qu
  • Mildred Felder
  • Zulmarie Perez Horta
  • Paul Sondel
Open Access
Poster presentation
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Keywords

Melanoma Gemcitabine Peritoneal Cavity Chemotherapy Regimen Antitumor Effect 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Our previous studies demonstrated that anti-CD40 mAb (anti-CD40) can synergize with CpG oligodeoxynucleotides (CpG) to mediate antitumor effects by activating myeloid cells, such as macrophages in tumor-bearing mice. Separate teams have shown that chemotherapy with gemcitabine (GEM) or 5-fluorouracil (5-FU) can reduce tumor-induced myeloid-derived suppressor cells (MDSC) in mice. In this study we asked if the same chemotherapy regimens with GEM or 5-FU will enhance the antitumor effect of anti-CD40 and CpG. Using the model of B16 melanoma growing intraperitoneally in syngeneic C57BL/6 mice, we show that these GEM or 5-FU treatment regimens either did not change or reduced, respectively, the number of MDSC in the peritoneal cavity of tumor-bearing mice. Treatment of mice with GEM or 5-FU did not significantly affect the antitumor function of macrophages as assessed in vitro. In vivo, treatment with these GEM or 5-FU regimens followed by anti-CD40/CpG resulted in antitumor effects similar to those of anti-CD40/CpG in the absence of GEM or 5-FU. Likewise, reduction of MDSC by in vivo anti-Gr-1 mAb treatment did not significantly affect anti-CD40/CpG antitumor responses. Together, the results show that the GEM or 5-FU chemotherapy regimens did not substantially affect the antitumor effects induced by anti-CD40/CpG immunotherapy.

Copyright information

© Rakhmilevich et al; licensee BioMed Central Ltd. 2013

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Authors and Affiliations

  • Alexander Rakhmilevich
    • 1
  • Xiaoyi Qu
    • 1
  • Mildred Felder
    • 1
  • Zulmarie Perez Horta
    • 1
  • Paul Sondel
    • 1
  1. 1.University of WisconsinMadisonUSA

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