ArticleScientific reports2017
Anti-Tumor Activity and Immunotherapeutic Potential of a Bisphosphonate Prodrug.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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
29 citing papers in PubMed, 53 citations in OpenAlex.
- Anti-tumor efficacy and Vδ2 T-cell activation via EGFR antibody-drug conjugates featuring novel aminobisphosphonates.Scientific reports · 2025Article
- Modulation of Human Colon Cell Activity by Synthetic Coumarin Derivatives Bearing a Phosphonate Group.Molecules (Basel, Switzerland) · 2025Article
- Human Vγ9Vδ2 T cells exhibit antifungal activity againstMicrobiology spectrum · 2024Article
- Human Vγ9Vδ2 T cell expansion and their cytotoxic responses against cholangiocarcinoma.Scientific reports · 2024Article
- Bisphosphonate-incorporated coatings for orthopedic implants functionalization.Materials today. Bio · 2023Review
- Anti‑metastatic activity of aromatic aminomethylidenebisphosphonates in a mouse model of 4T1 cell‑derived breast cancer.Oncology reports · 2023Article
- EBV latent membrane protein 1 augments γδ T cell cytotoxicity against nasopharyngeal carcinoma by induction of butyrophilin molecules.Theranostics · 2023Article
- Prodrugs of pyrophosphates and bisphosphonates: disguising phosphorus oxyanions.RSC medicinal chemistry · 2022Review
- Drug Delivery to the Bone Microenvironment Mediated by Exosomes: An Axiom or Enigma.International journal of nanomedicine · 2021Review
- New Progress in Improving the Delivery Methods of Bisphosphonates in the Treatment of Bone Tumors.Drug design, development and therapy · 2021Review
- PD-1 checkpoint blockade enhances adoptive immunotherapy by human Vγ2Vδ2 T cells against human prostate cancer.Oncoimmunology · 2021Article
- Review
- Structure-Activity Relationships of Butyrophilin 3 Ligands.ChemMedChem · 2020Review
- Three-Component Reaction of Diamines with Triethyl Orthoformate and Diethyl Phosphite and Anti-Proliferative and Antiosteoporotic Activities of the Products.Molecules (Basel, Switzerland) · 2020Article
- Comparison of a Novel Bisphosphonate Prodrug and Zoledronic Acid in the Induction of Cytotoxicity in Human Vγ2Vδ2 T Cells.Frontiers in immunology · 2020Article
- Phosphonate and Bisphosphonate Inhibitors of Farnesyl Pyrophosphate Synthases: A Structure-Guided Perspective.Frontiers in chemistry · 2020Review
- Nanoformulated Zoledronic Acid Boosts the Vδ2 T Cell Immunotherapeutic Potential in Colorectal Cancer.Cancers · 2019Article
- Application and design of esterase-responsive nanoparticles for cancer therapy.Drug delivery · 2019Review
- Critical Roles for Coiled-Coil Dimers of Butyrophilin 3A1 in the Sensing of Prenyl Pyrophosphates by Human Vγ2Vδ2 T Cells.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Phosphonate prodrugs: an overview and recent advances.Future medicinal chemistry · 2019Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Bisphosphonates have benefits in breast cancer and multiple myeloma patients and have been used with adoptive immunotherapy with γδ T cells expressing Vγ2 Vδ2 TCRs. Although treatment with γδ T cells is safe, it has shown limited efficacy. Present bisphosphonates stimulate γδ T cells but were designed to inhibit bone resorption rather than treating cancer and have limited oral absorption, tumor cell entry, and cause bone side effects. The development of phosphate and phosphonate nucleotide prodrugs has led to important drugs for hepatitis C and HIV. Using a similar approach, we synthesized bisphosphonate prodrugs and found that they efficiently limit tumor cell growth. Pivoxil bisphosphonate esters enter cells where esterases convert them to their active acids. The bisphosphonate esters stimulated γδ T cells to secrete TNF-α in response to a variety of tumor cells more efficiently than their corresponding acids. The most active compound, tetrakis-pivaloyloxymethyl 2-(thiazole-2-ylamino)ethylidene-1,1- bisphosphonate (7), specifically expanded γδ T cells and stimulated them to secrete interferon-γ and kill tumor cells. In preclinical studies, combination therapy with compound 7 and γδ T cells prolonged survival of mice inoculated with either human bladder cancer or fibrosarcoma cells. Therefore, bisphosphonate prodrugs could enhance the effectiveness of adoptive cancer immunotherapy with γδ T cells.
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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.