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Y S Zhu P J Kiley T J Donohue S Kaplan 《The Journal of biological chemistry》1986,261(22):10366-10374
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Respiratory and cardiovascular responses to exercise in the duck 总被引:1,自引:0,他引:1
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Robert Sarnovsky Tara Tendler Matheusz Makowski Maureen Kiley Antonella Antignani Roberta Traini Jingli Zhang Raffit Hassan David J. FitzGerald 《Cancer immunology, immunotherapy : CII》2010,59(5):737-746
Immunotoxins are antibody–toxin fusion proteins under development as cancer therapeutics. In early clinical trials, immunotoxins
constructed with domains II and III of Pseudomonas exotoxin (termed PE38), have produced a high rate of complete remissions
in Hairy Cell Leukemia and objective responses in other malignancies. Cholera exotoxin (also known as cholix toxin) has a
very similar three-dimensional structure to Pseudomonas exotoxin (PE) and when domains II and III of each are compared at
the primary sequence level, they are 36% identical and 50% similar. Here we report on the construction and activity of an
immunotoxin made with domains II and III of cholera exotoxin (here termed CET40). In cell viability assays, the CET40 immunotoxin
was equipotent to tenfold less active compared to a PE-based immunotoxin made with the same single-chain Fv. A major limitation
of toxin-based immunotoxins is the development of neutralizing antibodies to the toxin portion of the immunotoxin. Because
of structure and sequence similarities, we evaluated a CET40 immunotoxin for the presence of PE-related epitopes. In western
blots, three-of-three anti-PE antibody preparations failed to react with the CET40 immunotoxin. More importantly, in neutralization
studies neither these antibodies nor those from patients with neutralizing titers to PE38, neutralized the CET40-immunotoxin.
We propose that the use of modular components such as antibody Fvs and toxin domains will allow a greater flexibility in how
these agents are designed and deployed including the sequential administration of a second immunotoxin after patients have
developed neutralizing antibodies to the first. 相似文献
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