A novel tumor-vaccine cell therapy using bone marrow-derived dendritic cell type 1 and antigen-specific Th1 cells

Abstract

Dendritic cell (DC)-based tumor-vaccine therapy is a rational strategy for tumor immunotherapy. However, using this protocol, it is still difficult to induce long-term regression in established tumor-bearing mice. To overcome this problem we developed a novel tumor-vaccine therapy, combining inactivated tumor cells with bone marrow-derived DC type 1 (BMDC1) and antigen-specific T(h)1 cells. BALB/c mice were intradermally inoculated with A20-OVA tumor cells expressing ovalbumin (OVA) as a model tumor antigen. After A20-OVA tumor mass became palpable (6-8 mm), mice were treated with DC-based vaccine therapy in various protocols. A complete cure of tumor-bearing mice was induced only when mice were repeatedly vaccinated with inactivated A20-OVA cells, OVA-pulsed BMDC1 and OVA-specific T(h)1 cells. Regression of tumor cells was associated with induction of T(h)1/T(c)1-dominant antitumor immunity. Removal of one of these cellular components during vaccination resulted in failure to completely cure tumor-bearing mice. Moreover, BMDC2 cells could not replace the therapeutic effect of BMDC1 cells combined with T(h)1 cells. Thus, we propose a novel tumor-vaccine cell therapy using DC1 and T(h)1 cells.