Biomedical Engineering Reference
In-Depth Information
mAb or its Fab' fragment were also chemically coupled to PEGylated liposomes
(LPs) (Simard and Leroux 2010 ). Such a liposomal formulation has been demon-
strated to specifically recognize the CD33 cell surface antigen and promote the
efficient intracellular delivery of 1-b-D-arabinofuranosylcytosine (ara-C, anti-
AML agent) to human myeloid leukemia cells.
3.1.2
Anti-HER2 Antibody
Another popular antibody for tumor targeting is the anti-HER-2 (human epidermal
growth factor receptor-2) antibody (Mamot et al. 2005 ; Wu et al. 2004 ). Since
HER-2 is highly-expressed on the surface of many human pancreatic cancer cell
lines, it can be used as a therapeutic target. Therapeutic antibodies such as
Trastuzumab and Herceptin have been routinely applied in the clinical treatment of
breast cancer and leukemia (Chiu et al. 2004a ). A number of reports have shown
that the anti-HER2 antibody can be decorated on a nano-particle surface via avidin-
biotin or covalently conjugated to polymers (e.g. polyethylenimine PEI) through
different crosslinkers. Moreover, anti-HER2 Ab-mediated delivery of oligonucle-
otides encased in lipid nanoparticles was also shown to be capable of targeting
mammary carcinoma cells (Kirpotin et al. 2006 ). These modified nanocarriers were
effectively endocytosed by HER2-overexpressing cells. In addition, a multifunc-
tional anti-HER2 Ab conjugated magnetic gold nano-shell particle showed the
potential for targeted MR (magnetic resonance) photo-thermal therapy and tumor
imaging (Kim et al. 2006 ).
3.1.3
Anti-CD7 Antibody
CD7 (Cluster of Differentiation 7), a human transmembrane protein, is found on
thymocytes and the majority of human T cells. It has been documented that CD7 is
rapidly internalized after antibody binding. Several research groups have exploited
an anti-CD7 mAb and its recombinant single-chain Fv (scFvCD7) fragment for
targeted delivery. For example, a single-chain Fv fragment was genetically linked
to a truncated Pseudomonas exotoxin A fragment, thereby conferring restricted
specificity for CD7 positive cells (Peipp et al. 2002 ). The recombinant immuno-
toxin promoted apoptosis in two CD7-positive cell lines and provided a potent
inducer of apoptosis in acute leukemic T cells. In a similar manner, scFvCD7 was
genetically fused with sTRAIL (tumor necrosis factor-related apoptosis-inducing
ligand) (Bremer et al. 2005 ). As expected, treatment with scFvCD7 : sTRAIL spe-
cifically induced potent CD7-restricted apoptosis in a series of malignant T-cell
lines, with low toxicity for normal human blood and endothelial cells.
In addition to the targeted delivery of a toxin, the scFvCD7 Ab was recently used
for siRNA delivery in vitro and in vivo . Kumar et al. conjugated a Cys-modified
scFvCD7 with an oligo-9-arginine peptide to obtain a cell type specific siRNA
delivery system (scFvCD7-9R) (Kumar et al. 2008 ). A combination of siRNAs
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