INDUCTION OF ANTITUMOR-ACTIVITY BY IMMUNIZATION WITH FUSIONS OF DENDRITIC AND CARCINOMA-CELLS

Dendritic cells (DCs) are potent antigen-presenting cells that prime n aive cytotoxic T-cells (CTLs)(1). In this study, we have fused DCs wit h MC38 carcinoma cells. The fusion cells were positive for major histo compatibility (MHC) class I and II, costimulating molecules and interc ellular cell adhesion molecule-1 (ICAM-1). The results show that the f usion cells stimulate naive T cells in the primary mixed lymphocyte re action (MLR) and induce MC38 tumor-specific CTLs in vivo. Antibody-med iated depletion experiments demonstrate that induction of CD4(+) and C D8(+) CTLs protects against challenge with tumor cells. We also show t hat immunization with the fusion cells induces rejection of establishe d metastases. These findings represent the first demonstration that fu sions of DCs and tumor cells can be used in the treatment of cancer.