Tumor stromal cells have gained increasing attention as possible target for cancer therapy. Fibroblast activation protein (FAP) represents a cell surface antigen selectively expressed by reactive tumor stromal fibroblasts of various cancers. Here, we describe anti-FAP immunoliposomes as carrier systems for active targeting of FAP-expressing cells. As targeting ligand we used single-chain Fv (scFv) molecules cross-reacting with human and mouse FAP. These scFv molecules were genetically modified to express an additional cysteine residue at the C-terminus allowing a defined and site-directed conjugation. Coupling to Mal-PEG(2000)-DSPE containing liposomes resulted in sterically stabilized scFv immunoliposomes showing strong and specific binding to FAP-expressing cells. These immunoliposomes were highly stable when incubated under physiological conditions (human plasma, 37 degrees C). In addition, we could show that binding to FAP-expressing cells leads to internalization of intact liposomes into the endosomal compartment. Thus, these anti-FAP scFv immunoliposomes should be suitable for target cell-specific delivery and uptake of encapsulated drugs.
%0 Journal Article
%1 Baum2007
%A Baum, Patrick
%A Müller, Dafne
%A Rüger, Ronny
%A Kontermann, Roland E.
%D 2007
%J Journal of Drug Targeting
%K 2007 izi kontermann
%N 6
%P 399--406
%R 10.1080/10611860701453034
%T Single-chain Fv immunoliposomes for the targeting of fibroblast activation protein-expressing tumor stromal cells
%U https://www.ncbi.nlm.nih.gov/pubmed/17613658
%V 15
%X Tumor stromal cells have gained increasing attention as possible target for cancer therapy. Fibroblast activation protein (FAP) represents a cell surface antigen selectively expressed by reactive tumor stromal fibroblasts of various cancers. Here, we describe anti-FAP immunoliposomes as carrier systems for active targeting of FAP-expressing cells. As targeting ligand we used single-chain Fv (scFv) molecules cross-reacting with human and mouse FAP. These scFv molecules were genetically modified to express an additional cysteine residue at the C-terminus allowing a defined and site-directed conjugation. Coupling to Mal-PEG(2000)-DSPE containing liposomes resulted in sterically stabilized scFv immunoliposomes showing strong and specific binding to FAP-expressing cells. These immunoliposomes were highly stable when incubated under physiological conditions (human plasma, 37 degrees C). In addition, we could show that binding to FAP-expressing cells leads to internalization of intact liposomes into the endosomal compartment. Thus, these anti-FAP scFv immunoliposomes should be suitable for target cell-specific delivery and uptake of encapsulated drugs.
%Z Baum, PatrickMuller, DafneRuger, RonnyKontermann, Roland EengEnglandJ Drug Target. 2007 Jul;15(6):399-406. doi: 10.1080/10611860701453034 .
%7 2007/07/07
%@ 1061-186X (Print)
1026-7158 (Linking)
@article{Baum2007,
abstract = {Tumor stromal cells have gained increasing attention as possible target for cancer therapy. Fibroblast activation protein (FAP) represents a cell surface antigen selectively expressed by reactive tumor stromal fibroblasts of various cancers. Here, we describe anti-FAP immunoliposomes as carrier systems for active targeting of FAP-expressing cells. As targeting ligand we used single-chain Fv (scFv) molecules cross-reacting with human and mouse FAP. These scFv molecules were genetically modified to express an additional cysteine residue at the C-terminus allowing a defined and site-directed conjugation. Coupling to Mal-PEG(2000)-DSPE containing liposomes resulted in sterically stabilized scFv immunoliposomes showing strong and specific binding to FAP-expressing cells. These immunoliposomes were highly stable when incubated under physiological conditions (human plasma, 37 degrees C). In addition, we could show that binding to FAP-expressing cells leads to internalization of intact liposomes into the endosomal compartment. Thus, these anti-FAP scFv immunoliposomes should be suitable for target cell-specific delivery and uptake of encapsulated drugs.},
added-at = {2023-06-29T13:07:55.000+0200},
annote = {Baum, PatrickMuller, DafneRuger, RonnyKontermann, Roland EengEnglandJ Drug Target. 2007 Jul;15(6):399-406. doi: 10.1080/10611860701453034 .},
author = {Baum, Patrick and M{\"{u}}ller, Dafne and R{\"{u}}ger, Ronny and Kontermann, Roland E.},
biburl = {https://puma.ub.uni-stuttgart.de/bibtex/2af758bfac00a59ff43eaa827cc5741da/fabian},
doi = {10.1080/10611860701453034},
edition = {2007/07/07},
interhash = {2f6d8bf481e5fba7e7d1d62700ab2211},
intrahash = {af758bfac00a59ff43eaa827cc5741da},
isbn = {1061-186X (Print)
1026-7158 (Linking)},
issn = {1061186X},
journal = {Journal of Drug Targeting},
keywords = {2007 izi kontermann},
number = 6,
pages = {399--406},
pmid = {17613658},
timestamp = {2023-06-29T13:07:55.000+0200},
title = {{Single-chain Fv immunoliposomes for the targeting of fibroblast activation protein-expressing tumor stromal cells}},
url = {https://www.ncbi.nlm.nih.gov/pubmed/17613658},
volume = 15,
year = 2007
}
