ArticleJournal for immunotherapy of cancer2022
Targeting of colorectal cancer organoids with zoledronic acid conjugated to the anti-EGFR antibody cetuximab.
Article in Journal for immunotherapy of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 22 citations in OpenAlex.
- Emerging organoids and organoids-on-chip platforms for translational development of antibody‒drug conjugates and next-generation bioconjugates.Acta pharmaceutica Sinica. B · 2026Review
- γδ T cells in colorectal and liver cancer.Nature reviews. Gastroenterology & hepatology · 2026Review
- Review
- Antibody-drug conjugates in colorectal cancer: molecular design, preclinical advances, and translational challenges.Cancer chemotherapy and pharmacology · 2026Review
- Organoids: technology refining, current applications and future directions.Molecular biomedicine · 2026Review
- Monoclonal Antibodies and Derivatives: Therapeutic Tools for Cancer.Oncology research · 2026Review
- Nano-Engineered Cetuximab-Copper Complexes for Targeted Drug Delivery in Head and Neck Cancer.Current drug delivery · 2026Article
- Anti-tumor efficacy and Vδ2 T-cell activation via EGFR antibody-drug conjugates featuring novel aminobisphosphonates.Scientific reports · 2025Article
- Immune organoid for cancer immunotherapy.Acta pharmaceutica Sinica. B · 2025Review
- Mechanisms and Functions of γδ T Cells in Tumor Cell Recognition.Current oncology (Toronto, Ont.) · 2025Review
- Review
- Review
- Human γδ T cells in the tumor microenvironment: Key insights for advancing cancer immunotherapy.Molecules and cells · 2025Review
- Harnessing Organoid Platforms for Nanoparticle Drug Development.Drug design, development and therapy · 2025Review
- Medulloblastoma: biology and immunotherapy.Frontiers in immunology · 2025Review
- Progress of research on γδ T cells in colorectal cancer (Review).Oncology reports · 2024Review
- Generation of Novel Tumour-Selective SEA Superantigen-Based Peptides with Improved Safety and Efficacy for Precision Cancer Immunotherapy.International journal of molecular sciences · 2024Article
- Epidermal Growth Factor Receptor Targeting in Colorectal Carcinoma: Antibodies and Patient-Derived Organoids as a Smart Model to Study Therapy Resistance.International journal of molecular sciences · 2024Review
- Signaling pathways in colorectal cancer implications for the target therapies.Molecular biomedicine · 2024Review
- Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAntibody-drug conjugates (ADC) are essential therapeutic options to treat solid and hematological cancers. The anti-epidermal growth factor-receptor (EGFR) antibody cetuximab (Cet) is used for the therapy of colorectal carcinoma (CRC). Anti-CRC Vδ2 cytolytic T lymphocytes can be elicited by the priming of tumor cells with the aminobisphosphonate zoledronic acid (ZA) and consequent presentation of isopentenyl pyrophosphates through butyrophilin (BTN) family members such as BTN3A1 and BTN2A1. A major drawback that impairs the targeting of ZA to CRC is the bone tropism of aminobisphosphonates.
methodsThe phosphoric group of ZA was linked to free amino groups of Cet in the presence of imidazole following the labeling of phosphoric groups of DNA to amino groups of proteins. The generation of Cet-ZA ADC was confirmed by matrix assisted laser desorption ionization mass spectrometry and inductively coupled plasma-mass spectrometry analysis. Thirteen CRC organoids were obtained with a chemically defined serum-free medium in Geltrex domes. Proliferation and activation of cytolytic activity against CRC organoids by Vδ2 T cells was detected with flow cytometry, crystal violet and cytotoxic probe assays and image analysis. Immunohistochemistry and quantification of BTN3A1 or BTN2A1 expression and the number of tumor infiltrating Vδ2 T cells in CRC were performed by automatic immunostaining, whole slide scanning and computerized analysis of digital pathology imaging.
resultsThe novel ADC Cet-ZA was generated with a drug antibody ratio of 4.3 and displayed a reactivity similar to the unconjugated antibody. More importantly, patient-derived CRC organoids, or CRC tumor cell suspensions, could trigger the expansion of Vδ2 T cells from peripheral blood and tumor infiltrating lymphocytes when primed with Cet-ZA. Furthermore, Cet-ZA triggered Vδ2 T cell-mediated killing of CRC organoids. The expression of BTN3A1 and BTN2A1 was detected not only in CRC organoids but also in CRC specimens, together with a considerable amount of tumor infiltrating Vδ2 T cells.
conclusionsThese findings are proof of concept that the Cet-ZA ADC can be used to target specifically CRC organoids and may suggest a new experimental approach to deliver aminobisphosphonates to EGFR
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