PRIMING FOR T-CELL-MEDIATED REJECTION OF ESTABLISHED TUMORS BY CUTANEOUS DNA IMMUNIZATION

DNA immunization has been shown to elicit both antibody and CTL respon ses against antigens expressed by infectious organisms. Because CTL re sponses have been implicated in rejection of cancer, we investigated w hether DNA immunization by particle bombardment using a gene gun could induce CTL responses that were capable of rejecting tumors in mice. D NA immunization by particle bombardment using genes encoding beta-gala ctosidase and ovalbumin primed mice to generate CTLs in two genetic ba ckgrounds (DBA/2 and C57BL/6 strains, respectively). DNA immunization was more potent in inducing CTLs than immunization with an optimized r egimen of ovalbumin peptide plus immune adjuvant. Immunity induced by DNA immunization protected mice against s.c. challenge with tumors exp ressing the beta-galactosidase antigen. Tumors were rejected even when DNA immunization was started 3 or 7 days after tumor challenge as tum ors were becoming established. Tumor rejection required CD8(+) T cells , confirming a role for CTLs in vivo. These studies show that DNA immu nization by particle bombardment can efficiently induce CTL responses that are capable of rejecting even established tumors.