Topic
Immunotoxin
About: Immunotoxin is a research topic. Over the lifetime, 2424 publications have been published within this topic receiving 78722 citations. The topic is also known as: Immunotoxins & Immunotoxin.
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TL;DR: CAC10-vcMMAE was highly potent and selective against CD30+ tumor lines but was more than 300-fold less active on antigen-negative cells in SCID mouse xenograft models of anaplastic large cell lymphoma or Hodgkin disease, and was efficacious at doses as low as 1 mg/kg.
894 citations
TL;DR: BL22 can induce complete remissions in patients with hairy-cell leukemia that is resistant to treatment with purine analogues, including cladribine.
Abstract: Background Hairy-cell leukemia that is resistant to treatment with purine analogues, including cladribine, has a poor prognosis. We tested the safety and efficacy of an immunotoxin directed against a surface antigen that is strongly expressed by leukemic hairy cells. Methods RFB4(dsFv)-PE38 (BL22), a recombinant immunotoxin containing an anti-CD22 variable domain (Fv) fused to truncated pseudomonas exotoxin, was administered in a dose-escalation trial by intravenous infusion every other day for a total of three doses. Results Of 16 patients who were resistant to cladribine, 11 had a complete remission and 2 had a partial remission with BL22. The three patients who did not have a response received low doses of BL22 or had preexisting toxin-neutralizing antibodies. Of the 11 patients in complete remission, 2 had minimal residual disease in the bone marrow or blood. During a median follow-up of 16 months (range, 10 to 23), 3 of the 11 patients who had a complete response relapsed and were retreated; all of t...
522 citations
TL;DR: Anti-Tac(Fv)–PE40 was very cytotoxic to two interleukin-2 receptor-bearing human cell lines but was not cytotoxicity to receptor-negative cells, suggesting that the construction and expression of this single chain antibody toxin fusion protein in E coli is likely to be influenced by its carrier status.
Abstract: Antibodies and growth factors have been chemically coupled to different toxins to produce cytotoxic molecules that selectively kill cells bearing appropriate antigens or receptors. Antibody-toxin conjugates (immunotoxins) produced using conventional chemical coupling techniques have several undesirable characteristics. The smallest binding unit of an antibody is an Fv fragment which consists of a light and heavy chain variable domain. Recently, active single chain Fv fragments of antibodies have been produced in Escherichia coli by attaching the light and heavy chain variable domains together with a peptide linker. Here we describe the construction and expression in E. coli of a single chain antibody toxin fusion protein, anti-Tac(Fv)-PE40, in which the variable regions of anti-Tac, a monoclonal antibody to the p55 subunit of the human interleukin-2 receptor, are joined in peptide linkage to PE40, a modified form of Pseudomonas exotoxin lacking its binding domain. Anti-Tac(Fv)-PE40 was very cytotoxic to two interleukin-2 receptor-bearing human cell lines but was not cytotoxic to receptor-negative cells.
507 citations
TL;DR: The transferrin receptor, a cell membrane-associated glycoprotein involved in iron homeostasis and cell growth, has been explored as a target to deliver therapeutic agents into tumor cells by receptor-mediated endocytosis.
477 citations
TL;DR: Toxin lacking domain Ia is about 100-fold less toxic to mice than intact PE and should be a useful molecule for the construction of immunotoxins.
461 citations