Immunogenicity of Immunotoxins Containing Pseudomonas Exotoxin A: Causes, Consequences, and Mitigation
نویسندگان
چکیده
منابع مشابه
Recombinant anti-erbB2 immunotoxins containing Pseudomonas exotoxin.
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...
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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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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...
متن کاملInhibition of antibody response to Pseudomonas exotoxin and an immunotoxin containing Pseudomonas exotoxin by 15-deoxyspergualin in mice.
Immunotoxins are potent cell-killing agents that may be useful in the treatment of cancer. The early production of neutralizing antibodies to immunotoxins is one of the major limiting factors for their use in humans. 15-Deoxyspergualin (DSG), a derivative of spergualin, which is a metabolite of Bacillus laterosporus, has been found to have immunosuppressive activity in rodents, dogs, and primat...
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ژورنال
عنوان ژورنال: Frontiers in Immunology
سال: 2020
ISSN: 1664-3224
DOI: 10.3389/fimmu.2020.01261