ArticleScientific reports2015
Quantification of recombinant immunotoxin delivery to solid tumors allows for direct comparison of in vivo and in vitro results.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- An optimized integrin α6-targeted peptide capable of delivering toxins for melanoma treatment.Journal of translational medicine · 2025Article
- Ru(II) CONTAINING PHOTOSENSITIZERS FOR PHOTODYNAMIC THERAPY: A CRITIQUE ON REPORTING AND AN ATTEMPT TO COMPARE EFFICACY.Coordination chemistry reviews · 2022Article
- Reduced cytotoxicity by mutation of lysine 590 ofImmunotherapy advances · 2022Article
- Mesothelin-Targeted Recombinant Immunotoxins for Solid Tumors.Biomolecules · 2020Review
- Rapid Evaluation of Antibody Fragment Endocytosis for Antibody Fragment-Drug Conjugates.Biomolecules · 2020Article
- Engineered Anti-GPC3 Immunotoxin, HN3-ABD-T20, Produces Regression in Mouse Liver Cancer Xenografts Through Prolonged Serum Retention.Hepatology (Baltimore, Md.) · 2020Article
- Use of a Thermophile Desiccation-Tolerant Cyanobacterial Culture and Os Redox Polymer for the Preparation of Photocurrent Producing Anodes.Frontiers in bioengineering and biotechnology · 2020Article
- Tofacitinib enhances delivery of antibody-based therapeutics to tumor cells through modulation of inflammatory cells.JCI insight · 2019Article
- Monolith affinity chromatography for the rapid quantification of a single-chain variable fragment immunotoxin.Journal of separation science · 2018Article
- Selective cytotoxicity of a novel immunotoxin based on pulchellin A chain for cells expressing HIV envelope.Scientific reports · 2017Article
- Bacterial Toxins for Cancer Therapy.Toxins · 2017Review
- Mesothelin-targeted immunotoxin RG7787 has synergistic anti-tumor activity when combined with taxanes.Oncotarget · 2017Article
- Characterization of a re-engineered, mesothelin-targeted Pseudomonas exotoxin fusion protein for lung cancer therapy.Molecular oncology · 2016Article
- Wide Variability in the Time Required for Immunotoxins to Kill B Lineage Acute Lymphoblastic Leukemia Cells: Implications for Trial Design.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Article
- Actinomycin D enhances killing of cancer cells by immunotoxin RG7787 through activation of the extrinsic pathway of apoptosis.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Protection of the Furin Cleavage Site in Low-Toxicity Immunotoxins Based on Pseudomonas Exotoxin A.Toxins · 2016Article
- Reduced Shedding of Surface Mesothelin Improves Efficacy of Mesothelin-Targeting Recombinant Immunotoxins.Molecular cancer therapeutics · 2016Article
- Protein Kinase Inhibitor H89 Enhances the Activity of Pseudomonas Exotoxin A-Based Immunotoxins.Molecular cancer therapeutics · 2016Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Solid tumors present challenges for delivery of protein therapeutics; current methods cannot quantify the functional effects of these agents. RG7787 (anti-mesothelin recombinant immunotoxin) is highly cytotoxic to pancreatic cancer cell lines, but with limited activity in vivo. To investigate this discrepancy, we developed a flow cytometry method to quantify the amount of RG7787 internalized per cell in tumors and used it to analyze tumor responses by determining the number of molecules of RG7787 internalized per cell in vivo and comparing it to that needed to kill cells in vitro. At a maximum tolerated dose of 7.5 mg/kg, tumor cells in vivo internalized a wide range of RG7787 with the average amount equivalent to the amount that induced growth arrest in vitro. However, 20% of cells accumulated 20,300 ITs per cell, sufficient to kill cells in vitro. At 2.5 mg/kg the top 20% of cells internalized enough RG7787 to only induce growth arrest. These data are in agreement with tumor responses; 22% regression following a 7.5 mg/kg dose and growth stabilization following 2.5 mg/kg. Comparing amounts of RIT delivered in vivo and in vitro can explain tumor responses and should facilitate the development of more active immunotoxins and other antibody based agents.
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