Endoglin (CD105) is a target for an oral DNA vaccine against breast cancer.
Endoglin (CD105), a co-receptor in the TGF-beta receptor complex, is over-expressed on proliferating endothelial cells in the breast tumor neovasculature and thus offers an attractive target for anti-angiogenic therapy. Here we report the anti-angiogenic/anti-tumor effects achieved in a prophylactic setting with an oral DNA vaccine encoding murine endoglin, carried by double attenuated Salmonella typhimurium (dam-, AroA-) to a secondary lymphoid organ, i.e., Peyer's patches . We demonstrate that an endoglin vaccine elicited activation of antigen-presenting dendritic cells, coupled with immune responses mediated by CD8+ T cells against endoglin-positive target cells. Moreover, we observed suppression of angiogenesis only in mice administered with the endoglin vaccine as compared to controls. These data suggest that a CD8+ T cell-mediated immune response induced by this vaccine effectively suppressed dissemination of pulmonary metastases of D2F2 breast carcinoma cells presumably by eliminating proliferating endothelial cells in the tumor vasculature. It is anticipated that vaccine strategies such as this may contribute to future therapies for breast cancer.
Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Sung-Hyung
SH
Lee
Noriko
N
Mizutani
Masato
M
Mizutani
Yunping
Y
Luo
He
H
Zhou
Charles
C
Kaplan
Sung-Woo
SW
Kim
Rong
R
Xiang
Ralph A
RA
Reisfeld
D000284:Administration, Oral; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D000071063:Endoglin; D005260:Female; D007108:Immune Tolerance / Q000187:drug effects; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D008213:Lymphocyte Activation; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D010581:Peyer's Patches / Q000276:immunology; D012486:Salmonella typhimurium / Q000235:genetics; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use
D019496:Cancer Vaccines; D000071063:Endoglin; C502004:Eng protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D019444:Vaccines, DNA