Jianmei Hou1, Jiyan Liu1, Yang Li1, Xia Zhao2, Ling Tian1, Zhenyu Ding1, Yanjun Wen1, Ting Niu1, Fei Xiao1, Yanyan Lou1, Guang‐Hong Tan1, Hongxin Deng1, Jiong Li1, Jinliang Yang1, Yong-Qiu Mao1, Bing Kan1, Yang Wu1, Qiu Li1, Yuquan Wei1
1State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan,
2Department of Gynecology and Obstetrics, Second West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, People's Republic of China
Tóm tắt
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 individuallyresulted 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.
