INDUCTION OF T CELL RESPONSES AGAINST AUTOLOGOUS OVARIAN TUMORS WITH WHOLE TUMOR CELL LYSATE-PULSED DENDRITIC CELLS

Abstract

The loading of dendritic cells (DCs) with whole tumor celllysates may circumvent the facts that few tumor-specific antigens have beenidentified in human solid tumors. The present study was designed to investigatewhether ovarian cancer cells lysate-pulsed DCs activate T cell responses againstautologous ovarian tumors. Incubation of T cells with autologous tumor celllysate-pulsed DCs stimulated proliferation of autologous T cells. T cellsprimed by autologous tumor cell lysate-pulsed DCs showed significant killingactivity against autologous tumor cells, which could be blocked by anti-MHC-class-Iand anti-CD8 mAb. By contrast, T cells primed by autologous unpulsed DCs aloneor tumor lysates alone failed to exhibit significant killing activity. Inaddition, T cells primed by DCs pulsed with allogeneic tumor cell lysatesor with autologous normal cell lysate or by these cell lysates alone did notinduce the increase in the autologous tumor killing activity. As additionalcontrols, T cells stimulated with autologous tumor lysate-pulsed DCs expressno increase in the lysis of autologous monocytes, allogeneic ovarian tumorcells and other cell lines including K562, Daudi and Molt-4. Furthermore,T cells stimulated with autologous tumor lysate-pulsed DCs could produce theconsiderable amounts of cytokines such as GM-CSF, TNF-α and IFN-γ.The data in the present study suggest that whole tumor cell lysates-pulsedDCs could activate T cell responses against autologous ovarian tumor cells,and that these pulsed DCs may be used as a new approach for the specific immunotherapyof ovarian cancer patients.