Enhancement of Antitumor Activity by Combination of Tumor Lysate-Pulsed Dendritic Cells and Celecoxib in a Rat Glioma Model

Abstract

Using dendritic cell (DC)-based vaccines for treatment of gliomas has emerged as a meaningful and feasible treatment approach for inducing long-term survival, but this approach so far has failed to generate significant clinical responses. In the present study, we demonstrated that glioma lysate-pulsed DCs in combination with celecoxib, a selective cyclooxygenase 2 (COX-2) inhibitor, showed more significantly enhanced antitumor activity with increased apoptosis of tumor cells, reduced neovascularization, and developed a strong cytotoxic T lymphocyte (CTL) response in tumor-bearing rats. Celecoxib may reduce production of prostaglandin E2 and modulate the balance between T helper 1 (Th1) cytokines and T helper 2 (Th2) cytokines by increasing the pivotal Th1 cytokine interleukin-12 and reducing Th2 cytokine interleukin-10. Taken together, our results demonstrated that selective inhibition of COX-2 using celecoxib combined with DC-based immunotherapy could act as an important novel strategy for improving future treatment of malignant gliomas.