Article
Targeted drug delivery to mesothelioma cells using functionally selected internalizing human single-chain antibodies.
Department of Anesthesia, University of California San Francisco, San Francisco, CA 94110, USA.
Molecular Cancer Therapeutics (impact factor:
5.23).
04/2008;
7(3):569-78.
DOI:10.1158/1535-7163.MCT-07-2132
Source: PubMed
-
Article: Toward selection of internalizing antibodies from phage libraries.
[show abstract] [hide abstract]
ABSTRACT: Antibodies which bind cell surface receptors in a manner whereby they are endocytosed are useful molecules for the delivery of drugs, toxins, or DNA into the cytosol of mammalian cells for therapeutic applications. Traditionally, internalizing antibodies have been identified by screening hybridomas. For this work, we studied a human scFv (C6.5) which binds ErbB2 to determine the feasibility of directly selecting internalizing antibodies from phage libraries and to identify the most efficient display format. Using wild-type C6.5 scFv displayed monovalently on a phagemid, we demonstrate that anti-ErbB2 phage antibodies can undergo receptor-mediated endocytosis. Using affinity mutants and dimeric diabodies of C6.5 displayed as either single copies on a phagemid or multiple copies on phage, we define the role of affinity, valency, and display format on phage endocytosis and identify the factors that lead to the greatest enrichment for internalization. Phage displaying bivalent diabodies or multiple copies of scFv were more efficiently endocytosed than phage displaying monomeric scFv and recovery of infectious phage was increased by preincubation of cells with chloroquine. Measurement of phage recovery from within the cytosol as a function of applied phage titer indicates that it is possible to select for endocytosable antibodies, even at the low concentrations that would exist for a single phage antibody member in a library of 10(9).Biochemical and Biophysical Research Communications 03/1999; 255(2):386-93. · 2.48 Impact Factor -
Article: Development of ligand-targeted liposomes for cancer therapy.
[show abstract] [hide abstract]
ABSTRACT: The continued evolution of targeted liposomal therapeutics has resulted in new agents with remarkable antitumour efficacy and relatively mild toxicity profiles. A careful selection of the ligand is necessary to reduce immunogenicity, retain extended circulation lifetimes, target tumour-specific cell surface epitopes, and induce internalisation and subsequent release of the therapeutic substance from the liposome. Methods for assembling targeted liposomes, including a novel micellar insertion technology, for incorporation of targeting molecules that efficiently transforms a non-targeted liposomal therapeutic to a targeted one, greatly assist the translation of targeted liposome technology into the clinic. Targeting strategies with liposomes directed at solid tumours and vascular targets are discussed. The authors believe the development of ligand-targeted liposomes is now in the advanced stage and offers unique and important advantages among other targeted therapies. Anti-HER2 immunoliposomal doxorubicin is awaiting Phase I clinical trials, the results of which should provide new insights into the promise of ligand-targeted liposomal therapies.Expert opinion on therapeutic targets 09/2004; 8(4):335-53. · 3.72 Impact Factor -
Article: Mesothelin: a new target for immunotherapy.
[show abstract] [hide abstract]
ABSTRACT: Mesothelin is a differentiation antigen present on normal mesothelial cells and overexpressed in several human tumors, including mesothelioma and ovarian and pancreatic adenocarcinoma. The mesothelin gene encodes a precursor protein that is processed to yield the 40-kDa protein, mesothelin, attached to the cell membrane by a glycosylphosphatidyl inositol linkage and a 31-kDa shed fragment named megakaryocyte-potentiating factor. The biological function of mesothelin is not known. Mesothelin is a promising candidate for tumor-specific therapy, given its limited expression in normal tissues and high expression in several cancers. SS1(dsFv)PE38 is a recombinant anti-mesothelin immunotoxin that is undergoing clinical evaluation in patients with mesothelin-expressing tumors. There is evidence that mesothelin is an immunogenic protein and could be exploited as a therapeutic cancer vaccine. A soluble mesothelin variant has been identified and could be a useful tumor marker for malignant mesotheliomas.Clinical Cancer Research 07/2004; 10(12 Pt 1):3937-42. · 7.74 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed.
The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual
current impact factor.
Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence
agreement may be applicable.
Keywords
antibodies stain mesothelioma cells
anticancer drug development
control cells
current treatments
immunoliposomes encapsulating
internalizing antibodies
internalizing function
internalizing scFvs
intracellular delivery
intracellular drug delivery
mesothelioma cell lines
mesothelioma cells
naive human single-chain
sarcomatous mesothelioma cells
scFv-targeted immunoliposomes
target mesothelioma-associated cell surface antigens
therapeutic agents
tumor antigens
tumor susceptibility
vitro
