ArticleJournal of controlled release : official journal of the Controlled Release Society2014
Combination of antibody targeting and PTD-mediated intracellular toxin delivery for colorectal cancer therapy.
Article in Journal of controlled release : official journal of the Controlled Release Society, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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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.
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Who cites it
26 citing papers in PubMed, 52 citations in OpenAlex.
- Membrane-Traversing Peptides: Mechanistic Landscapes, Assays, and Applications.Chemical reviews · 2026Review
- Exploring the Chemical Features and Biomedical Relevance of Cell-Penetrating Peptides.International journal of molecular sciences · 2024Review
- Aiming the magic bullet: targeted delivery of imaging and therapeutic agents to solid tumors by pHLIP peptides.Frontiers in pharmacology · 2024Review
- Review
- Emerging Landscape of Cell-Penetrating Peptide-Mediated Organelle Restoration and Replacement.ACS pharmacology & translational science · 2023Review
- Molecularly engineered tumor acidity-responsive plant toxin gelonin for safe and efficient cancer therapy.Bioactive materials · 2022Article
- Review
- Transient Inhibition of Trastuzumab-Tumor Binding to Overcome the "Binding-Site Barrier" and Improve the Efficacy of a Trastuzumab-Gelonin Immunotoxin.Molecular cancer therapeutics · 2022Article
- Cell Penetrating Peptides Conjugated to Anti-Carcinoembryonic Antigen "Catch-and-Release" Monoclonal Antibodies Alter Plasma and Tissue Pharmacokinetics in Colorectal Cancer Xenograft Mice.Bioconjugate chemistry · 2022Article
- The role of cell-penetrating peptides in potential anti-cancer therapy.Clinical and translational medicine · 2022Review
- Targeted Delivery of Endosomal Escape Peptides to Enhance Immunotoxin Potency and Anti-cancer Efficacy.The AAPS journal · 2022Article
- Antibody-Based Immunotoxins for Colorectal Cancer Therapy.Biomedicines · 2021Review
- TAT for Enzyme/Protein Delivery to Restore or Destroy Cell Activity in Human Diseases.Life (Basel, Switzerland) · 2021Review
- Decoding the proteome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for cell-penetrating peptides involved in pathogenesis or applicable as drug delivery vectors.Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2020Article
- Advances on Tumor-Targeting Delivery of Cytotoxic Proteins.ACS pharmacology & translational science · 2020Review
- An energy-blocking nanoparticle decorated with anti-VEGF antibody to reverse chemotherapeutic drug resistance.RSC advances · 2019Article
- Recent Advances in Cell Penetrating Peptide-Based Anticancer Therapies.Molecules (Basel, Switzerland) · 2019Review
- High-yield expression in3 Biotech · 2019Article
- Improved Protein Toxin Delivery Based on ATTEMPTS Systems.Current drug targets · 2018Review
- Cell Penetrating Peptides as Molecular Carriers for Anti-Cancer Agents.Molecules (Basel, Switzerland) · 2018Review
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 3 countries.
Funding
Abstract
The bottlenecks of current chemotherapy in the treatment of colorectal cancer lie in the ineffectiveness of the existing anti-cancer small molecule drugs as well as the dose-limiting toxicity caused by the nonselective action on normal tissues by such drugs. To address these problems, we introduce a novel therapeutic strategy based on tumor targeting using a non-internalizing anti-carcinoembryonic antigen (CEA) monoclonal antibody (mAb) and intracellular delivery of the extremely potent yet cell-impermeable protein toxin gelonin via the aid of a cell-penetrating peptide (also termed as protein transduction domain; PTD). A chimeric TAT-gelonin fusion protein was genetically engineered, and it displayed remarkably enhanced anti-cancer activity against human colorectal cancer cells, with IC50 values being several orders of magnitude lower than the unmodified gelonin. On the other hand, a chemically synthesized conjugate of heparin and a murine anti-CEA mAb, T84.66 (termed T84.66-Hep) was found able to bind highly specifically to CEA over-expressing LS174T colorectal cancer cells. When mixing together, TAT-gelonin and T84.66-Hep could associate tightly and automatically through an electrostatic interaction between the cationic TAT and anionic heparin. In preliminary in vivo studies using LS174T s.c. xenograft tumor bearing mouse, selective and significantly augmented (58-fold) delivery of TAT-gelonin to the tumor target was observed, when compared with administration of TAT-gelonin alone. More importantly, efficacy studies also revealed that only the TAT-gelonin/T84.66-Hep complex yielded a significant inhibition of tumor growth (46%) without causing gelonin-induced systemic toxicity. Overall, this study suggested a generic strategy to effectively yet safely deliver potent PTD-modified protein toxins to the tumor.
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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.