The clinical application of synthetic tumor peptide‐based vaccines is currently limited to patients with specified major histocompatibility complex (MHC) class I alleles. Such logistic limitations may be overcome using tumor gene‐based approaches. Here we describe the effective generation of dendritic cells (DC) expressing tumor peptide‐MHC complexes as a result of particle‐mediated transfer of genes encoding tumor‐associated antigens (TAA). Bone marrow‐derived DC were transfected with plasmid DNA encoding the tumor‐associated viral antigen E₇ derived from human papilloma virus (HPV) 16. When applied as a vaccine, these genetically modified DC induced antigen‐specific CD8⁺ cyto‐toxic T lymphocytes (CTL) in vivo and promoted the rejection of a subsequent, normally lethal challenge with an HPV 16‐transformed tumor cell line. Of greatest interest, immunization of mice with syngeneic DC genetically modified to enhance their presentation of a constitutive “self” epitope derived from the tumor‐suppressor gene product p53 caused a significant reduction in the in vivo growth of a chemically induced p53‐positive sarcoma. These results suggest that cancer vaccines consisting of DC genetically modified to express TAA of viral or “self” origin effectively induce antitumor immunity in vivo.