Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.3.1.108 (
TAT
)
2,389
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Human monoclonal antibodies are promising agents for the development of more selective anticancer therapeutics. However, the tumor-targeting efficiency of most anticancer antibodies is severely limited by their poor penetration into the tumor mass. Recent studies have shown that a peptide derived from the HIV TAT protein could improve the distribution of cytoplasmic reporter proteins when administered systemically as fusion proteins or cross-linked chimeras. In this article, we tested by quantitative biodistribtution analysis whether conjugation to
TAT
peptides could improve the tumor targeting properties of scFv(L19)-Cys: an engineered human antibody fragment specific for the
ED-B
domain of fibronectin, a marker located in the modified extracellular matrix surrounding tumor neovasculature. Our results show that
TAT
peptides, consisting either of L-amino acids or D-amino acids, can efficiently transduce target cells when conjugated to fluorophores and/or antibody fragments, suggesting a receptor-independent cell entry mechanism. However, conjugation of scFv(L19)-Cys to
TAT
peptides resulted in a severely reduced tumor targeting performance compared to the unconjugated antibody, as measured in murine F9 teratocarcinoma-bearing mice, after intravenous injection of the radiolabeled antibody preparations. Our results outline the usefulness of
TAT
peptides for the efficient in vitro transduction of cells with globular proteins. In particular, the use of
TAT
peptides composed of D-amino acids may significantly reduce proteolytic degradation. At the same time, the poor biodistribution properties of antibody-
TAT
conjugates cast doubts over the applicability of this methodology for the delivery of biopharmaceuticals in vivo.
...
PMID:Quantitation of the tumor-targeting properties of antibody fragments conjugated to cell-permeating HIV-1 TAT peptides. 1212 Nov 27
