Combination of low-dose gemcitabine and recombinant quail vascular endothelial growth factor receptor-2 as a vaccine induces synergistic antitumor activities

Jian Mei Hou, Ji Yan Liu, Li Yang, Xia Zhao, Ling Tian, Zhen Yu Ding, Yan Jun Wen, Ting Niu, Fei Xiao, Yan Yan Lou, Guang Hong Tan, Hong Xin Deng, Jiong Li, Jin Liang Yang, Yong Qiu Mao, Yu Quan Wei

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Vascular endothelial growth factor receptor-2 (VEGFR-2) has been shown to play a major role in inducing the full spectrum of VEGF biological response which is essential for tumor angiogenesis. We have demonstrated that immunotherapy of tumors with a vaccine based on quail homologous VEGFR-2 (qVEGFR) was effective in providing both protective and therapeutic antitumor immunity in several tumor models in mice. The purpose of this study was to determine whether the combination therapy of low-dose gemcitabine with qVEGFR as a vaccine could inhibit tumor growth to a greater extent. To test this concept, H22 hepatoma and Lewis lung carcinoma models were established in BALB/c mice and C57BL/6 mice, respectively. Mice were treated with either qVEGFR as a protein vaccine, gemcitabine, or both agents together. qVEGFR or low-dose chemotherapy treatment individually resulted in tumor inhibition to a certain extent. Remarkably, the combination therapy resulted in synergistic antitumor activity. Histological examination revealed that there was endothelial deposition of immunoglobulins within tumor tissues from mice treated with vaccine or combination therapy, especially intratumor angiogenesis was suppressed more significantly for the combination group. Also, ELISPOT analysis showed that mice treated with either qVEGFR alone or in combination with low-dose chemotherapy produced similar amount of anti-VEGFR antibody-producing B cells, which suggested that low-dose gemcitabine did not suppress the host's immune response, but potentiated the antitumor activity of the qVEGFR vaccine. Furthermore, TUNEL staining demonstrated a significant increase in the number of TUNEL-positive cells in the combination group compared with those of other groups. The observations may provide a new bio-chemotherapeutic approach for cancer.

Original languageEnglish (US)
Pages (from-to)81-87
Number of pages7
JournalOncology
Volume69
Issue number1
DOIs
StatePublished - Aug 1 2005

Keywords

  • Gemcitabine
  • Tumor
  • Vaccine
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Hou, J. M., Liu, J. Y., Yang, L., Zhao, X., Tian, L., Ding, Z. Y., Wen, Y. J., Niu, T., Xiao, F., Lou, Y. Y., Tan, G. H., Deng, H. X., Li, J., Yang, J. L., Mao, Y. Q., & Wei, Y. Q. (2005). Combination of low-dose gemcitabine and recombinant quail vascular endothelial growth factor receptor-2 as a vaccine induces synergistic antitumor activities. Oncology, 69(1), 81-87. https://doi.org/10.1159/000087303