ArticleMolecular cancer2015
Human anti-CAIX antibodies mediate immune cell inhibition of renal cell carcinoma in vitro and in a humanized mouse model in vivo.
Article in Molecular cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.
- Development of humanized mouse with patient-derived xenografts for cancer immunotherapy studies: A comprehensive review.Cancer science · 2021Pooled it
- Discovery of tumor antigens in renal cell carcinoma and prospects for clinical application.Frontiers in immunology · 2026Review
- Carbonic Anhydrase IX and Cyclooxygenase-2 Regulation in Renal Cell Carcinoma and Impact on Therapeutic Efficiency of Anti-CAIX CAR T cells.Current topics in medicinal chemistry · 2026Article
- Engineering CRISPR System-Based Bacterial Outer Membrane Vesicle Potentiates T Cell Immunity for Enhanced Cancer Immunotherapy.Advanced materials (Deerfield Beach, Fla.) · 2025Article
- Biologically targeted dual adaptive and innate nano-Immunotherapy for clear cell renal cell carcinoma treatment.Molecular cancer · 2025Article
- Advances in Therapeutic Cancer Vaccines, Their Obstacles, and Prospects Toward Tumor Immunotherapy.Molecular biotechnology · 2025Review
- NK cells in renal cell carcinoma and its implications for CAR-NK therapy.Frontiers in cell and developmental biology · 2025Review
- Preclinical Evaluation of virus-like particle Vaccine Against Carbonic Anhydrase IX Efficacy in a Mouse Breast Cancer Model System.Molecular biotechnology · 2024Article
- Article
- Immune-restoring CAR-T cells display antitumor activity and reverse immunosuppressive TME in a humanized ccRCC mouse model.iScience · 2024Article
- A case of lung adenocarcinoma expressing carbonic anhydrase IX and cluster of differentiation 10 antigen combined with renal clear cell carcinoma.CytoJournal · 2024Article
- Therapeutic cancer vaccines: advancements, challenges, and prospects.Signal transduction and targeted therapy · 2023Review
- Lactate oxidase nanocapsules boost T cell immunity and efficacy of cancer immunotherapy.Science translational medicine · 2023Article
- Humanized mouse models for immuno-oncology research.Nature reviews. Clinical oncology · 2023Review
- The roles of metabolic profiles and intracellular signaling pathways of tumor microenvironment cells in angiogenesis of solid tumors.Cell communication and signaling : CCS · 2022Review
- Review
- Novel humanized monoclonal antibodies for targeting hypoxic human tumors via two distinct extracellular domains of carbonic anhydrase IX.Cancer & metabolism · 2022Article
- Preclinical models for development of immune-oncology therapies.Immuno-oncology insights · 2022Article
- Establishment of a ccRCC patient-derived chick chorioallantoic membrane model for drug testing.Frontiers in medicine · 2022Article
- Critical evaluation of an autologous peripheral blood mononuclear cell-based humanized cancer model.PloS one · 2022Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCarbonic anhydrase (CA) IX is a surface-expressed protein that is upregulated by the hypoxia inducible factor (HIF) and represents a prototypic tumor-associated antigen that is overexpressed on renal cell carcinoma (RCC). Therapeutic approaches targeting CAIX have focused on the development of CAIX inhibitors and specific immunotherapies including monoclonal antibodies (mAbs). However, current in vivo mouse models used to characterize the anti-tumor properties of fully human anti-CAIX mAbs have significant limitations since the role of human effector cells in tumor cell killing in vivo is not directly evaluated.
methodsThe role of human anti-CAIX mAbs on CAIX(+) RCC tumor cell killing by immunocytes or complement was tested in vitro by antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC) and antibody-dependent cellular phagocytosis (ADCP) as well as on CAIX(+) RCC cellular motility, wound healing, migration and proliferation. The in vivo therapeutic activity mediated by anti-CAIX mAbs was determined by using a novel orthotopic RCC xenograft humanized animal model and analyzed by histology and FACS staining.
resultsOur studies demonstrate the capacity of human anti-CAIX mAbs that inhibit CA enzymatic activity to result in immune-mediated killing of RCC, including nature killer (NK) cell-mediated ADCC, CDC, and macrophage-mediated ADCP. The killing activity correlated positively with the level of CAIX expression on RCC tumor cell lines. In addition, Fc engineering of anti-CAIX mAbs was shown to enhance the ADCC activity against RCC. We also demonstrate that these anti-CAIX mAbs inhibit migration of RCC cells in vitro. Finally, through the implementation of a novel orthotopic RCC model utilizing allogeneic human peripheral blood mononuclear cells in NOD/SCID/IL2Rγ(-/-) mice, we show that anti-CAIX mAbs are capable of mediating human immune response in vivo including tumor infiltration of NK cells and activation of T cells, resulting in inhibition of CAIX(+) tumor growth.
conclusionsOur findings demonstrate that these novel human anti-CAIX mAbs have therapeutic potential in the unmet medical need of targeted killing of HIF-driven CAIX(+)RCC. The orthotopic tumor xenografted humanized mouse provides an improved model to evaluate the in vivo anti-tumor capabilities of fully human mAbs for RCC therapy.
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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.