ArticleBlood2009
A protease-resistant immunotoxin against CD22 with greatly increased activity against CLL and diminished animal toxicity.
Article in Blood, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
101 citing papers in PubMed.
- Phase II trial of recombinant immunotoxin RFB4(dsFv)-PE38 (BL22) in patients with hairy cell leukemia.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2009Trial
- Novel PE-DT-fusion toxin enhances internalization and target-dependently restores the cytotoxicity of recombinant immunotoxins.Frontiers in pharmacology · 2026Article
- In vitro evidence of HER2-selective cytotoxicity by scFv(Herceptin)-PE-STXA immunotoxin in gastric cancer cells.Biochemistry and biophysics reports · 2025Article
- Introduction of Reactive Thiol Handles into Tyrosine-Tagged Proteins through Enzymatic Oxidative Coupling.Journal of the American Chemical Society · 2025Article
- Intracellular trafficking of furin enhances cellular intoxication by recombinant immunotoxins based on Pseudomonas exotoxin A.Biology open · 2025Article
- Antibody-Drug Conjugates (ADCs): current and future biopharmaceuticals.Journal of hematology & oncology · 2025Review
- Article
- Evaluation of the Safety of A Novel Anti-HER2 Immunotoxin Containing Modified Fragment ofIranian journal of biotechnology · 2025Article
- Exploring protein-protein ligation approaches for the cytosolic delivery of antigens using AIP56.Frontiers in cellular and infection microbiology · 2025Article
- Hosts and Heterologous Expression Strategies of Recombinant Toxins for Therapeutic Purposes.Toxins · 2023Review
- Improving the cytotoxicity of immunotoxins by reducing the affinity of the antibody in acidic pH.Journal of translational medicine · 2023Article
- Synthesis of an Anti-CD7 Recombinant Immunotoxin Based on PE24 in CHO andInternational journal of molecular sciences · 2022Article
- Strategies to mitigate the on- and off-target toxicities of recombinant immunotoxins: an antibody engineering perspective.Antibody therapeutics · 2022Review
- GPC1-Targeted Immunotoxins Inhibit Pancreatic Tumor Growth in Mice via Depletion of Short-lived GPC1 and Downregulation of Wnt Signaling.Molecular cancer therapeutics · 2022Article
- Comparison of CD3e Antibody and CD3e-sZAP Immunotoxin Treatment in Mice Identifies sZAP as the Main Driver of Vascular Leakage.Biomedicines · 2022Article
- CD3e-immunotoxin spares CD62LFrontiers in immunology · 2022Article
- Reduced cytotoxicity by mutation of lysine 590 ofImmunotherapy advances · 2022Article
- Targeted Toxins for the Treatment of Prostate Cancer.Biomedicines · 2021Review
- Soluble Cytoplasmic Expression and Purification of Immunotoxin HER2(scFv)-PE24B as a Maltose Binding Protein Fusion.International journal of molecular sciences · 2021Article
- Natural and Designed Toxins for Precise Therapy: Modern Approaches in Experimental Oncology.International journal of molecular sciences · 2021Review
41 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
Abstract
Immunotoxins based on Pseudomonas exotoxin A (PE) are promising anticancer agents that combine a variable fragment (Fv) from an antibody to a tumor-associated antigen with a 38-kDa fragment of PE (PE38). The intoxication pathway of PE immunotoxins involves receptor-mediated internalization and trafficking through endosomes/lysosomes, during which the immunotoxin undergoes important proteolytic processing steps but must otherwise remain intact for eventual transport to the cytosol. We have investigated the proteolytic susceptibility of PE38 immunotoxins to lysosomal proteases and found that cleavage clusters within a limited segment of PE38. We subsequently generated mutants containing deletions in this region using HA22, an anti-CD22 Fv-PE38 immunotoxin currently undergoing clinical trials for B-cell malignancies. One mutant, HA22-LR, lacks all identified cleavage sites, is resistant to lysosomal degradation, and retains excellent biologic activity. HA22-LR killed chronic lymphocytic leukemia cells more potently and uniformly than HA22, suggesting that lysosomal protease digestion may limit immunotoxin efficacy unless the susceptible domain is eliminated. Remarkably, mice tolerated doses of HA22-LR at least 10-fold higher than lethal doses of HA22, and these higher doses exhibited markedly enhanced antitumor activity. We conclude that HA22-LR advances the therapeutic efficacy of HA22 by using an approach that may be applicable to other PE-based immunotoxins.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.