Publication
Selective targeting of adenovirus to alpha(v)beta(3) integrins, VEGFR2 and Tie2 endothelial receptors by angio-adenobodies
Haisma, H. J., Kamps, G. K., Bouma, A., Geel, T. M., Rots, M. G., Kariath, A. & Bellu, A. R., 31-May-2010, In : International Journal of Pharmaceutics. 391, 1-2, p. 155-161 7 p.Research output: Contribution to journal › Article › Academic › peer-review
APA
Author
Harvard
Standard
Selective targeting of adenovirus to alpha(v)beta(3) integrins, VEGFR2 and Tie2 endothelial receptors by angio-adenobodies. / Haisma, Hidde J.; Kamps, Gera K.; Bouma, Arend; Geel, Tessa M.; Rots, Marianne G.; Kariath, Anu; Bellu, Anna Rita.
In: International Journal of Pharmaceutics, Vol. 391, No. 1-2, 31.05.2010, p. 155-161.Research output: Contribution to journal › Article › Academic › peer-review
Vancouver
BibTeX
}
RIS
TY - JOUR
T1 - Selective targeting of adenovirus to alpha(v)beta(3) integrins, VEGFR2 and Tie2 endothelial receptors by angio-adenobodies
AU - Haisma, Hidde J.
AU - Kamps, Gera K.
AU - Bouma, Arend
AU - Geel, Tessa M.
AU - Rots, Marianne G.
AU - Kariath, Anu
AU - Bellu, Anna Rita
PY - 2010/5/31
Y1 - 2010/5/31
N2 - Tumor angiogenesis is a prominent mechanism, driving the development and progression of solid tumors and the formation of cancer cell metastasis. Newly formed tumor vessels represent an elective target for the activity and the delivery of cancer therapeutics. We targeted adenovirus (Ad5) to endothelial receptors which are up-regulated during the formation of new blood vessels, to enhance the efficiency of anticancer gene therapy applications.Bifunctional angio-adenobodies were constructed by the fusion of a single chain antibody directed against the adenoviral fiber knob, to different peptides recognizing the alpha(v)beta(3) integrins, VEGFR2 and Tie2 receptors on endothelial cells. The angio-adenobodies were coupled to the adenoviral vector, containing luciferase and GFP as reporter genes.In vitro data showed selective targeting of the Ad5 to the endothelial receptors both in mouse (H5V) and human cell lines (HUVEC). H5V cells, refractory to Ad5 infection, showed high level of luciferase expression when cells were infected with targeted virus. Viral transgene expression increased in HUVEC cells when cells were infected with Ad5 conjugated with angio-adenobody thereby demonstrating the affinity of the peptides for human endothelial cells also. In vivo data obtained from mice bearing a C26 colon carcinoma subcutaneously show viral transgene expression only in tumors infected with angio-adenobodies retargeted adenovirus.The results of the present study demonstrate that endothelial targeted angio-adenobodies represent a versatile tool to direct adenovirus from its native receptors to the integrins a alpha(v)beta(3), VEGFR2 and Tie2 receptors that are fundamental in many angiogenesis related diseases such as cancer. (C) 2010 Elsevier B.V. All rights reserved.
AB - Tumor angiogenesis is a prominent mechanism, driving the development and progression of solid tumors and the formation of cancer cell metastasis. Newly formed tumor vessels represent an elective target for the activity and the delivery of cancer therapeutics. We targeted adenovirus (Ad5) to endothelial receptors which are up-regulated during the formation of new blood vessels, to enhance the efficiency of anticancer gene therapy applications.Bifunctional angio-adenobodies were constructed by the fusion of a single chain antibody directed against the adenoviral fiber knob, to different peptides recognizing the alpha(v)beta(3) integrins, VEGFR2 and Tie2 receptors on endothelial cells. The angio-adenobodies were coupled to the adenoviral vector, containing luciferase and GFP as reporter genes.In vitro data showed selective targeting of the Ad5 to the endothelial receptors both in mouse (H5V) and human cell lines (HUVEC). H5V cells, refractory to Ad5 infection, showed high level of luciferase expression when cells were infected with targeted virus. Viral transgene expression increased in HUVEC cells when cells were infected with Ad5 conjugated with angio-adenobody thereby demonstrating the affinity of the peptides for human endothelial cells also. In vivo data obtained from mice bearing a C26 colon carcinoma subcutaneously show viral transgene expression only in tumors infected with angio-adenobodies retargeted adenovirus.The results of the present study demonstrate that endothelial targeted angio-adenobodies represent a versatile tool to direct adenovirus from its native receptors to the integrins a alpha(v)beta(3), VEGFR2 and Tie2 receptors that are fundamental in many angiogenesis related diseases such as cancer. (C) 2010 Elsevier B.V. All rights reserved.
KW - Adenovirus
KW - Angiogenesis
KW - alpha(v)beta(3) Integrins
KW - VEGFR2
KW - Tie2
KW - SINGLE-CHAIN DIABODY
KW - TUMOR ANGIOGENESIS
KW - GENE-TRANSFER
KW - BISPECIFIC ANTIBODIES
KW - THERAPEUTIC TARGET
KW - IN-VIVO
KW - CANCER
KW - VECTORS
KW - CELLS
KW - DELIVERY
U2 - 10.1016/j.ijpharm.2010.02.032
DO - 10.1016/j.ijpharm.2010.02.032
M3 - Article
VL - 391
SP - 155
EP - 161
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
SN - 0378-5173
IS - 1-2
ER -
ID: 5097095