An oral DNA vaccine against human carcinoembryonic antigen (CEA) prevents growth and dissemination of Lewis lung carcinoma in CEA transgenic mice.
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.
Niethammer
A G
AG
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Primus
F J
FJ
Xiang
R
R
Dolman
C S
CS
Ruehlmann
J M
JM
Ba
Y
Y
Gillies
S D
SD
Reisfeld
R A
RA
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*
D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen; D015395:Histocompatibility Antigens Class I; D019444:Vaccines, DNA; D018664:Interleukin-12