Protein Kinase Inhibitor H89 Enhances the Activity of Pseudomonas Exotoxin A–Based Immunotoxins
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منابع مشابه
Protein Kinase Inhibitor H89 Enhances the Activity of Pseudomonas Exotoxin A-Based Immunotoxins.
HA22 (Moxetumomab pasudotox) is a recombinant immunotoxin (RIT), composed of an anti-CD22 Fv fused to a truncated portion of Pseudomonas exotoxin A. HA22 is in clinical trials to treat patients with hairy cell leukemia and acute lymphoblastic leukemia (ALL). LMB-11 is an improved variant of HA22 with reduced immunogenicity, has a longer half-life in the blood and high activity in vitro and in a...
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Immunotoxins were made using five different murine monoclonal antibodies to the human erbB2 gene product and LysPE40, a 40-kDa recombinant form of Pseudomonas exotoxin (PE) lacking its cell-binding domain. All five conjugates were specifically cytotoxic to cancer cell lines overexpressing erbB2 protein. The most active conjugate was e23-LysPE40, generated by chemical crosslinking of anti-erbB2 ...
متن کاملActivity of immunotoxins constructed with modified Pseudomonas exotoxin A lacking the cell recognition domain.
Pseudomonas exotoxin (PE) contains three domains whose functions are cell recognition, membrane translocation, and ADP ribosylation of elongation factor 2. PE40 is a form of PE which is missing the cell recognition domain. To study the properties of PE40, it was expressed in Escherichia coli using a vector which contains a T7 phage promoter, an OmpA signal sequence, and that portion of the PE g...
متن کاملThe protein kinase A inhibitor H89 acts on cell morphology by inhibiting Rho kinase.
The small GTPase RhoA can retract cell extensions by acting on two Rho kinases (ROCKs). Activated protein kinase A (PKA) inhibits RhoA and induces extensions. The isoquinoline H89 inhibits PKA and thus should prevent the inactivation of RhoA. In kinase assays, H89 has been recently found to inactivate a ROCK-II also. Because H89 may be able to exert opposite effects on cell extensions, we have ...
متن کاملProtection of the Furin Cleavage Site in Low-Toxicity Immunotoxins Based on Pseudomonas Exotoxin A
Recombinant immunotoxins (RITs) are fusions of an Fv-based targeting moiety and a toxin. Pseudomonas exotoxin A (PE) has been used to make several immunotoxins that have been evaluated in clinical trials. Immunogenicity of the bacterial toxin and off-target toxicity have limited the efficacy of these immunotoxins. To address these issues, we have previously made RITs in which the Fv is connecte...
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ژورنال
عنوان ژورنال: Molecular Cancer Therapeutics
سال: 2016
ISSN: 1535-7163,1538-8514
DOI: 10.1158/1535-7163.mct-15-0828