Abstract:
:Antibody targeted cytoplasmic delivery of drugs is difficult to achieve as antigen-antibody interaction results in the payload being directed to the endosomal compartment. However, Sendai viral envelopes can bring about cytoplasmic delivery due to F-protein mediated membrane fusion. In this study we have generated and fused a recombinant scFv directed to the onco-fetal antigen, the Placental isozyme of Alkaline Phosphatase (PAP) with the trans-membrane and part of the cytoplasmic domain of the Sendai F protein (F(TMC)). Reconstituted virosomes, having both the fusion protein as well as the native F-protein were able to specifically bind and deliver drugs to PAP expressing cells. About 75% of the delivery was cytoplasmic in nature. Hence, this immuno-virosome, which is devoid of the comparatively more toxic HN protein, has the novel ability to combine specific antibody mediated targeting with cytoplasmic delivery. The scFv ensured specific binding to PAP expressing cells, without cross reacting with the other isozymes of alkaline phosphatase. The advantages of cytoplasmic delivery would include reduced degradation and lowered immunogenicity of the payload and carrier. The ubiquitous expression of PAP on a variety of cancers like seminoma, choriocarcinoma, cervical and breast cancers also suggests its potential usefulness in a number of malignancies.
journal_name
Curr Mol Medjournal_title
Current molecular medicineauthors
Kumar M,Mani P,Pratheesh P,Chandra S,Jeyakkodi M,Chattopadhyay P,Sarkar DP,Sinha Sdoi
10.2174/1566524015666150505155949subject
Has Abstractpub_date
2015-01-01 00:00:00pages
386-400issue
4eissn
1566-5240issn
1875-5666pii
CMM-EPUB-67045journal_volume
15pub_type
杂志文章abstract::The currently available knowledge of factors that dictate the development and progression as well as the clinical outcome of colorectal cancers (CRC) is mainly derived from Western countries. Considerable number of publications document different incidence rates and contrasting clinical features of CRC in various grou...
journal_title:Current molecular medicine
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更新日期:2009-08-01 00:00:00
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更新日期:2016-01-01 00:00:00
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journal_title:Current molecular medicine
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更新日期:2007-06-01 00:00:00
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更新日期:2011-11-01 00:00:00
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更新日期:2004-02-01 00:00:00
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abstract::Pancreatic Adenocarcinoma (PDAC) is one of the most deadly malignant tumors worldwide. A variety of mechanisms are involved in PDAC biological behaviors, of which, the mechanisms of immune escape may be a pivotal hallmark. HLA-G is a tolerant molecule implicated in tumor escape and serves as a prognostic biomarker in ...
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更新日期:2004-12-01 00:00:00
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