A33scFv–cytosine deaminase: a recombinant protein construct for antibody-directed enzyme-prodrug therapy

Deckert, P. Markus; Renner, Christoph; Cohen, Lawrence E.; Jungbluth, Achim A.; Ritter, Gerd; Bertino, Joseph R.; Old, Lloyd J.; Welt, Sydney

doi:10.1038/sj.bjc.6600751

Cited by 34 publications

(29 citation statements)

References 9 publications

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“…Although genetically fused antibody/enzyme conjugates can be produced, we, and others, have observed that the production levels of these conjugates are frequently very low [7][8][9]. In fact, our initial attempt to produce an antibody-FCU1 fusion protein in myeloma cells was unsuccessful because of low production levels (unpublished data).…”

Section: Discussionmentioning

confidence: 99%

“…As an alternative approach, recombinant DNA technology could be used to prepare homogeneous antibody-enzyme fusion proteins. However, for reasons we have yet to understand, production levels of such fusion proteins are often very low, limiting their use in clinical (or sometimes even animal) studies [7][8][9]. In addition, this strategy requires that a different fusion protein be produced for every antibody/enzyme combination, which is cumbersome, and there may be a decrease in activity of one or both covalently linked partners.…”

Section: U N C O R R E C T E D P R O O Fmentioning

confidence: 99%

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A human biotin acceptor domain allows site-specific conjugation of an enzyme to an antibody-avidin fusion protein for targeted drug delivery

Asai

Trinh

et al. 2005

Biomolecular Engineering

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We have previously constructed an antibody-avidin (Av) fusion protein, anti-transferrin receptor (TfR) IgG3-Av, which can deliver biotinylated molecules to cells expressing the TfR. We now describe the use of the fusion protein for antibody-directed enzyme prodrug therapy (ADEPT). The 67 amino acid carboxyl-terminal domain (P67) of human propionyl-CoA carboxylase a subunit can be metabolically biotinylated at a fixed lysine residue. We genetically fused P67 to the carboxyl terminus of the yeast enzyme FCU1, a derivative of cytosine deaminase that can convert the non-toxic prodrug 5-fluorocytosine to the cytotoxic agent 5-fluorouracil. When produced in Escherichia coli cells overexpressing a biotin protein ligase, the FCU1-P67 fusion protein was efficiently mono-biotinylated. In the presence of 5-fluorocytosine, the biotinylated fusion protein conjugated to anti-rat TfR IgG3-Av efficiently killed rat Y3-Ag1.2.3 myeloma cells in vitro, while the same protein conjugated to an irrelevant (anti-dansyl) antibody fused to Av showed no cytotoxic effect. Efficient tumor cell killing was also observed when E. coli purine nucleoside phosphorylase was similarly targeted to the tumor cells in the presence of the prodrug 2-fluoro-2 0 -deoxyadenosine. These results suggest that when combined with P67-based biotinylation, anti-TfR IgG3-Av could serve as a universal delivery vector for targeted chemotherapy of cancer. # 2004 Published by Elsevier B.V.

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Section: Discussionmentioning

confidence: 99%

Section: U N C O R R E C T E D P R O O Fmentioning

confidence: 99%

A human biotin acceptor domain allows site-specific conjugation of an enzyme to an antibody-avidin fusion protein for targeted drug delivery

Asai

Trinh

et al. 2005

Biomolecular Engineering

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“…115 This antibody fragment is known to target the A33 antigen, which is expressed by the majority of primary and metastatic colorectal tumors. 116 The A33scFv-targeted NPs were selectively internalized by colorectal SW1222 xenograft tumors over non-A33-expressing cells. Subsequently, these tumors underwent laser-assisted photothermal treatment (808 nm, 5 W − 1 cm − 2 ) which adversely affected more than 65% of A33-expressing SW1222 cells by damaging the ECM and cytoplasmic acidophilia.…”

Section: Colorectal Cancermentioning

confidence: 99%

Targeted superparamagnetic iron oxide nanoparticles for early detection of cancer: Possibilities and challenges

Bakhtiary

Saei

Hajipour

et al. 2016

Nanomedicine: Nanotechnology, Biology and Medicine

152

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Nanomedicine, the integration of nanotechnological tools in medicine demonstrated promising potential to revolutionize the diagnosis and treatment of various human health conditions. Nanoparticles (NPs) have shown much promise in diagnostics of cancer, especially since they can accommodate targeting molecules on their surface, which search for specific tumor cell receptors upon injection into the blood stream. This concentrates the NPs in the desired tumor location. Furthermore, such receptor-specific targeting may be exploited for detection of potential metastases in an early stage. Some NPs, such as superparamagnetic iron oxide NPs (SPIONs), are also compatible with magnetic resonance imaging (MRI), which makes their clinical translation and application rather easy and accessible for tumor imaging purposes. Furthermore, multifunctional and/or theranostic NPs can be used for simultaneous imaging of cancer and drug delivery. In this review article, we will specifically focus on the application of SPIONs in early detection and imaging of major cancer types.From the Clinical Editor: Super-paramagnetic iron oxide nanoparticles (SPIONs) have been reported by many to be useful as an MRI contrast agent in the detection of tumors. To further enhance the tumor imaging, SPIONs can be coupled with tumor targeting motifs. In this article, the authors performed a comprehensive review on the current status of using targeted SPIONS in tumor detection and also the potential hurdles to overcome. © 2015 Elsevier Inc. All rights reserved. 1 A significant improvement in cancer survival has been noted over the past three decades for most cancer types. This notable and continuous decrement in tumor fatality is related to advanced development in prevention, early diagnosis and therapeutic approaches and decrease in overall prevalence of smoking.1 Early detection of cancer, especially before cancer cells metastasize, is critical for cancer diagnosis, because early stage cancers can be treated more effectively. However, early-stage diagnosis has been difficult to achieve in most cases since clinical symptoms tend to show up at later stages. Therefore, minimally-and non-invasive methods for early detection of cancer are urgently needed in the field. In this regard, many SPION-based systems are under development for more sensitive imaging and earlier detection of tumors. Since non-targeted SPION species cannot readily differentiate cancer tissues from normal tissues, second-generation SPIONs have been developed which are equipped with targeting moieties that can recognize Nanomedicine: Nanotechnology, Biology, and Medicine 12 (2016) 287 -307

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“…CD enzyme was modified to obtain targeting specificity by conjugation with antibodies that were able to direct enzyme to the tumor cell surfaces (Senter et al, 1991;Wallace et al, 1994;Deckert et al, 2003). These modifications have been shown to increase antitumor activities in combination with prodrug 5-FC partly due to increase in intratumoral drug concentrations.…”

Section: Transduction Of Yeast Cytosine Deam Inase M Ediated By Hiv-1mentioning

confidence: 99%

Transduction of yeast cytosine deaminase mediated by HIV-1 Tat basic domain into tumor cells induces chemosensitivity to 5-fluorocytosine

Lee

Ryu²,

Kim³

et al. 2004

Exp Mol Med

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A33scFv–cytosine deaminase: a recombinant protein construct for antibody-directed enzyme-prodrug therapy

Cited by 34 publications

References 9 publications

A human biotin acceptor domain allows site-specific conjugation of an enzyme to an antibody-avidin fusion protein for targeted drug delivery

A human biotin acceptor domain allows site-specific conjugation of an enzyme to an antibody-avidin fusion protein for targeted drug delivery

Targeted superparamagnetic iron oxide nanoparticles for early detection of cancer: Possibilities and challenges

Transduction of yeast cytosine deaminase mediated by HIV-1 Tat basic domain into tumor cells induces chemosensitivity to 5-fluorocytosine

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