Low-dose docetaxel enhances the anti-tumour efficacy of a human umbilical vein endothelial cell vaccine

Abstract

Our previous studies have indicated that human umbilical vein endothelial cell (HUVEC) vaccination appears to be a potentially promising anti-angiogenesis therapy, but the modest therapeutic anti-tumour efficiency limits its clinical use. This highlights the importance of identifying more potent therapeutic HUVEC vaccine strategies for clinical testing. In the present study, the immune-modulating doses of docetaxel (DOC) was combined with 1 × 106 viable HUVECs as a means to enhance the therapeutic anti-tumour efficiency of the HUVEC vaccine. Our results demonstrated that 5 mg/kg DOC administrated prior to HUVEC vaccine could most effectively assist HUVEC vaccine to display a remarkable suppression of tumour growth and metastasis as wells as a prolongation of survival time in a therapeutic procedure. CD31 immunohistochemical analysis of the excised tumours confirmed a significant reduction in vessel density after treatment with the HUVEC vaccine with 5 mg/kg DOC. Additionally, an increased HUVEC-specific antibody level, activated CTLs and an elevated IFN-γ level in cultured splenocytes were revealed after treatment with HUVEC vaccine with 5 mg/kg DOC. Finally, 5 mg/kg DOC coupled with the HUVEC vaccine led to induction of significant increases in CD8+T cells and decrease in Tregs in the tumour microenvironment. Taken together, all the results verified that 5 mg/kg DOC could assist HUVEC vaccine to elicit strong HUVEC specific humoral and cellular responses, which could facilitate the HUVEC vaccine-mediated inhibition of cancer growth and metastasis. These findings provide the immunological rationale for the combined use of immune-modulating doses of DOC and HUVEC vaccines in patients with cancer.