ArticleClinical cancer research : an official journal of the American Association for Cancer Research2011
Pentostatin plus cyclophosphamide safely and effectively prevents immunotoxin immunogenicity in murine hosts.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 42 citations in OpenAlex.
- Major cancer regressions in mesothelioma after treatment with an anti-mesothelin immunotoxin and immune suppression.Science translational medicine · 2013Trial
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- Target Therapy in Malignant Pleural Mesothelioma: Hope or Mirage?International journal of molecular sciences · 2023Review
- Antibody-Based Approaches to Target Pancreatic Tumours.Antibodies (Basel, Switzerland) · 2022Review
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- Advances on Delivery of Cytotoxic Enzymes as Anticancer Agents.Molecules (Basel, Switzerland) · 2022Review
- Translational development of a tumor junction opening technology.Scientific reports · 2022Article
- Harnessing the Membrane Translocation Properties of AB Toxins for Therapeutic Applications.Toxins · 2021Review
- Review
- Mesothelin-Targeted Recombinant Immunotoxins for Solid Tumors.Biomolecules · 2020Review
- From Malignant Progression to Therapeutic Targeting: Current Insights of Mesothelin in Pancreatic Ductal Adenocarcinoma.International journal of molecular sciences · 2020Review
- Strategies to Reduce the Immunogenicity of Recombinant Immunotoxins.The American journal of pathology · 2018Review
- The Role of Mesothelin as a Diagnostic and Therapeutic Target in Pancreatic Ductal Adenocarcinoma: A Comprehensive Review.Targeted oncology · 2018Review
- Tolerogenic nanoparticles restore the antitumor activity of recombinant immunotoxins by mitigating immunogenicity.Proceedings of the National Academy of Sciences of the United States of America · 2018Review
- Target therapy: new drugs or new combinations of drugs in malignant pleural mesothelioma.Journal of thoracic disease · 2018Review
- Anti-tumor activity of anthrax toxin variants that form a functional translocation pore by intermolecular complementation.Oncotarget · 2017Article
- Mesothelin Immunotherapy for Cancer: Ready for Prime Time?Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2016Review
- Engineered human angiogenin mutations in the placental ribonuclease inhibitor complex for anticancer therapy: Insights from enhanced sampling simulations.Protein science : a publication of the Protein Society · 2016Article
- Solid tumor therapy by selectively targeting stromal endothelial cells.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Tumor Targeting and Drug Delivery by Anthrax Toxin.Toxins · 2016Review
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
purposeThe success of immunotoxin therapy of cancer is limited by host production of neutralizing antibodies, which are directed toward the Pseudomonas exotoxin A (PE) component. In this proof-of-principle study using a well-established murine model, we hypothesized that a newly developed immune depletion regimen consisting of pentostatin plus cyclophosphamide would abrogate anti-immunotoxin reactivity. EXPERIMENTAL
designBALB/c hosts were injected weekly with recombinant immunotoxin (RIT) SS1P, which is an antimesothelin Fv antibody fragment genetically fused to a 38 kDa portion of PE, and has been evaluated in clinical trials. Experimental cohorts received induction chemotherapy consisting of pentostatin (P) plus cyclophosphamide (C) prior to initial RIT exposure; some cohorts received further maintenance PC therapy of varying intensity just prior to each weekly RIT challenge. Cohorts were monitored for T, B, myeloid cell depletion, and for total anti-SS1P antibody (Ab) formation.
resultsControls uniformly developed anti-SS1P Ab after the third RIT exposure. Induction PC therapy reduced the frequency of hosts with anti-SS1P Ab. Abrogation of antibody generation was improved by maintenance PC therapy: nearly 100% of recipients of intensive PC maintenance were free of anti-SS1P Ab after 9 weekly RIT doses. The most effective PC regimen yielded the greatest degree of host B-cell depletion, moderate T-cell depletion, and minimal myeloid cell depletion.
conclusionsInduction and maintenance PC chemotherapy safely prevented anti-immunotoxin antibody formation with uniform efficacy. These data suggest that immunotoxin therapy might be used in combination with pentostatin plus cyclophosphamide chemotherapy to improve the targeted therapy of cancer.
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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.