title: An oral DNA vaccine against human carcinoembryonic antigen (CEA) prevents growth and dissemination of Lewis lung carcinoma in CEA transgenic mice.
abstract: A DNA vaccine encoding human carcinoembryonic antigen (CEA) broke peripheral T-cell tolerance toward this tumor self-antigen expressed by Lewis lung carcinoma stably transduced with CEA in C57BL/6J mice transgenic for CEA. This vaccine, delivered by oral gavage with an attenuated strain of Salmonella typhimurium (SL7207), and boosted with an antibody-IL2 fusion protein, induced tumor-protective immunity mediated by MHC class I antigen-restricted CD8(+) T cells, resulting in eradication of subcutaneous tumors in 100% of mice and prevention of experimental pulmonary metastases in 75% of experimental animals. Both CTL and antigen-presenting dendritic cells were activated as indicated by a decisive increase in their respective activation markers CD2, CD25, CD28 as well as CD48 and CD80. The antitumor effects of this CEA-based DNA vaccine obtained in prophylactic settings, suggest that this approach could lead to the rational design of effective treatment modalities for human lung cancer.
authors.affiliation: Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: A G
authors.initials: AG
authors.lastname: Niethammer
authors.forename: F J
authors.initials: FJ
authors.lastname: Primus
authors.forename: R
authors.initials: R
authors.lastname: Xiang
authors.forename: C S
authors.initials: CS
authors.lastname: Dolman
authors.forename: J M
authors.initials: JM
authors.lastname: Ruehlmann
authors.forename: Y
authors.initials: Y
authors.lastname: Ba
authors.forename: S D
authors.initials: SD
authors.lastname: Gillies
authors.forename: R A
authors.initials: RA
authors.lastname: Reisfeld
mesh_terms: D000284:Administration, Oral; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000276:immunology*; D018827:Carcinoma, Lewis Lung / Q000517:prevention & control / Q000556:secondary; D003713:Dendritic Cells / Q000502:physiology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D018664:Interleukin-12 / Q000008:administration & dosage; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen; D015395:Histocompatibility Antigens Class I; D019444:Vaccines, DNA; D018664:Interleukin-12