The alpha v beta 3 integrin as a tumor homing ligand for lymphocytes.

Details

Serval ID
serval:BIB_32740
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The alpha v beta 3 integrin as a tumor homing ligand for lymphocytes.
Journal
European Journal of Immunology
Author(s)
Legler D.F., Johnson-Léger C., Wiedle G., Bron C., Imhof B.A.
ISSN
0014-2980[print], 0014-2980[linking]
Publication state
Published
Issued date
2004
Volume
34
Number
6
Pages
1608-1616
Language
english
Abstract
Despite the presence of tumor-specific effector cells in the circulation of cancer patients, the immune response of the majority of these patients is not sufficient to prevent the growth and spread of their tumors. That tumor cells can be killed in vitro by tumor-reactive cytotoxic T cells is testimony to the fact that the tumors are not inherently resistant to T cell killing, but rather that there is a failure in immune recognition and effector cell activation. Many reasons for this failure of the body's defense system have been suggested, including the inability of tumor-reactive lymphocytes to migrate to tumor tissue. Here we designed a strategy to improve homing of primary lymphocytes into vascularized tumors. As a homing molecule we selected the integrin alpha v beta 3 since it is expressed by angiogenic vascular endothelium in tumors. To promote lymphocyte adhesion to alpha v beta 3 we "painted" primary lymphocytes with a recombinant, glycosylphosphatidylinositol-linked high-affinity ligand for alpha v beta 3. These painted lymphocytes specifically bound to alpha v beta 3 in vitro and homed to vascularized, solid tumors in vivo. This novel strategy may provide a significant advance in anti-tumor treatment such as adoptive immune therapy.
Keywords
Amino Acid Sequence, Animals, Base Sequence, Carcinoma, Lewis Lung/immunology, Carcinoma, Lewis Lung/therapy, Cell Adhesion/immunology, Flow Cytometry, Humans, Immunotherapy, Adoptive/methods, Integrin alphaVbeta3/immunology, Jurkat Cells, Mice, Mice, Inbred C57BL, Molecular Sequence Data, Receptors, Lymphocyte Homing/immunology, Recombinant Proteins, T-Lymphocytes/immunology
Pubmed
Web of science
Create date
19/11/2007 12:31
Last modification date
20/08/2019 13:18
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