Endoglin (CD105) is a target for an oral DNA vaccine against breast cancer

被引:57
作者
Lee, Sung-Hyung [1 ]
Mizutani, Noriko [1 ]
Mizutani, Masato [1 ]
Luo, Yunping [1 ]
Zhou, He [1 ]
Kaplan, Charles [1 ]
Kim, Sung-Woo [1 ]
Xiang, Rong [1 ]
Reisfeld, Ralph A. [1 ]
机构
[1] Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA
关键词
DNA vaccine; endoglin; breast cancer; anti-angiogenesis;
D O I
10.1007/s00262-006-0155-5
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:1565 / 1574
页数:10
相关论文
共 37 条
[1]   The sponge/Matrigel angiogenesis assay [J].
Akhtar N. ;
Dickerson E.B. ;
Auerbach R. .
Angiogenesis, 2002, 5 (1-2) :75-80
[2]   Antiangiogenic tumour therapy: will it work? [J].
Augustin, HG .
TRENDS IN PHARMACOLOGICAL SCIENCES, 1998, 19 (06) :216-222
[3]  
CHEIFETZ S, 1992, J BIOL CHEM, V267, P19027
[4]   Role of transforming growth factor-β signaling in cancer [J].
de Caestecker, MP ;
Piek, E ;
Roberts, AB .
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2000, 92 (17) :1388-1402
[5]   CD105 is important for angiogenesis: evidence and potential applications [J].
Duff, SE ;
Li, CG ;
Garland, JM ;
Kumar, S .
FASEB JOURNAL, 2003, 17 (09) :984-992
[6]  
FOLKMAN J, 1971, NEW ENGL J MED, V285, P1182
[7]   Tumor angiogenesis and tissue factor [J].
Folkman, J .
NATURE MEDICINE, 1996, 2 (02) :167-168
[8]   Can mosaic tumor vessels facilitate molecular diagnosis of cancer? [J].
Folkman, J .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (02) :398-400
[9]   Endoglin (CD105): a powerful therapeutic target on tumor-associated angiogenetic blood vessels [J].
Fonsatti, E ;
Altomonte, M ;
Nicotra, MR ;
Natali, PG ;
Maio, M .
ONCOGENE, 2003, 22 (42) :6557-6563
[10]   Endoglin (CD105): A target for anti-angiogenetic cancer therapy [J].
Fonsatti, E ;
Altomonte, M ;
Arslan, P ;
Maio, M .
CURRENT DRUG TARGETS, 2003, 4 (04) :291-296