IMMUNOTHERAPEUTIC POTENTIAL OF TUMOR ANTIGEN-PULSED AND UNPULSED DENDRITIC CELLS GENERATED FROM MURINE BONE-MARROW

Dendritic cells (DC) are highly efficient antigen-presenting cells abl e to capture, process, and present antigens to naive and primed T-cell s. In this study, we have investigated the ability of DC, derived from murine bone marrow and pulsed with tumor cell extracts, to induce reg ression of preexisting tumors. In an experimental model of B16 melanom a in B6 mice, a significant reduction in metastatic nodules in the lun gs was observed in tumor-bearing animals treated with either DC alone or DC pulsed with tumor extracts. Kinetic studies demonstrate that the efficacy of these tumor vaccines is inversely related to tumor burden . In this model, tumor-specific cytotoxic T-cells (CTL) could also be induced in vitro from spleen cells derived from tumor-bearing animals treated with DC pulsed with tumor extracts. Untreated mice had no CTL. Furthermore, DC alone elicited tumor-specific CTL responses in tumor- bearing mice, but not in naive mice. Immune cell depletion experiments show that the therapeutic effects of DC are primarily mediated by CD8 (+) T-cells, while CD4(+) T-cells and NK cells are involved in DC-medi ated antitumor immunity to a limited extent. These results illustrate the potential use of DC and DC pulsed with tumor extracts as potent th erapeutic reagents for cancer and provide a rationale for using DC in vivo to eliminate disseminated tumors or residual tumor deposits follo wing surgery. (C) 1997 Academic Press.