ArticleClinical cancer research : an official journal of the American Association for Cancer Research2015
Nonblocking Monoclonal Antibody Targeting Soluble MIC Revamps Endogenous Innate and Adaptive Antitumor Responses and Eliminates Primary and Metastatic Tumors.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 43 citations in OpenAlex.
- Targeting the NKG2D axis in head and neck squamous cell carcinoma: from molecular insights to clinical applications.Cancer cell international · 2026Review
- Targeting NKG2D/NKG2DL axis in cancer immunotherapy: mechanisms and therapeutic applications.Journal of translational medicine · 2026Review
- Insights into ectodomain shedding as a novel target in natural killer cell-based immunotherapy for cancer.Frontiers in immunology · 2026Review
- Unleashing NK cells for cancer immunotherapy in lung cancer: biologic challenges and clinical advances.Journal of experimental & clinical cancer research : CR · 2025Review
- A potential mechanism of tumor immune escape: Regulation and application of soluble natural killer group 2 member D ligands (Review).Oncology reports · 2024Review
- Natural killer cells in cancer immunotherapy.MedComm · 2024Review
- The Human Soluble NKG2D Ligand Differentially Impacts Tumorigenicity and Progression in Temporal and Model-Dependent Modes.Biomedicines · 2024Article
- Clearing soluble MIC reverses the impaired function of natural killer cells from patients with multiple myeloma.Journal for immunotherapy of cancer · 2024Article
- NKG2D signaling regulates IL-17A-producing γδT cells in mice to promote cancer progression.Discovery immunology · 2022Article
- The MICA-NKG2D axis in clear cell renal cell carcinoma bolsters MICA as target in immuno-oncology.Oncoimmunology · 2022Article
- MULT1-Encoding DNA Alleviates Schistosomiasis-Associated Hepatic Fibrosis via Modulating Cellular Immune Response.Journal of inflammation research · 2022Article
- Role of NK Cells in Tumor Progression.Experientia supplementum (2012) · 2022Article
- The Advantages and Challenges of Anticancer Dendritic Cell Vaccines and NK Cells in Adoptive Cell Immunotherapy.Vaccines · 2021Review
- The Biological Role and Therapeutic Potential of NK Cells in Hematological and Solid Tumors.International journal of molecular sciences · 2021Review
- Tumor-derived NKG2D ligand sMIC reprograms NK cells to an inflammatory phenotype through CBM signalosome activation.Communications biology · 2021Article
- Review
- Leveraging NKG2D Ligands in Immuno-Oncology.Frontiers in immunology · 2021Review
- Could Harnessing Natural Killer Cell Activity Be a Promising Therapy for Prostate Cancer?Critical reviews in immunology · 2021Review
- Review
- Antibody targeting tumor-derived soluble NKG2D ligand sMIC reprograms NK cell homeostatic survival and function and enhances melanoma response to PDL1 blockade therapy.Journal of hematology & oncology · 2020Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
purposeThe human tumor-derived soluble MHC I-chain-related molecule (sMIC) is highly immune suppressive in cancer patients and correlates with poor prognosis. However, the therapeutic effect of targeting sMIC has not been determined, due to the limitation that mice do not express homologs of human MIC. This study is to evaluate the therapeutic effect of a monoclonal antibody (mAb) targeting sMIC in a clinically relevant transgenic animal model. EXPERIMENTAL
designWe treated the engineered MIC-expressing "humanized" TRAMP/MIC bitransgenic mice at advanced disease stages with a sMIC-neutralizing nonblocking anti-MIC mAb and assessed the therapeutic efficacy and associated mechanisms.
resultsA sMIC-neutralizing nonblocking anti-MIC mAb effectively induced regression of primary tumors and eliminated metastasis without inducing systemic toxicity. The therapeutic effect is conferred by revamping endogenous antitumor immune responses, exemplified by restoring natural killer (NK) cell homeostasis and function, enhancing susceptibility of MIC(+)-tumor cells to NK cell killing, reviving and sustaining antigen-specific CD8 T-cell responses, augmenting CD4 T cells to Th1 responses, priming dendritic cells for antigen presentation, and remodeling tumor microenvironment to be more immune reactive.
conclusionsTherapy with a sMIC-neutralizing nonblocking anti-MIC mAb can effectuate antitumor immune responses against advanced MIC(+) tumors. Our study provided strong rationale for translating sMIC-neutralizing therapeutic mAb into clinics, either alone or in combination with current ongoing standard immunotherapies.
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