Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2016
Checkpoint Inhibition of KIR2D with the Monoclonal Antibody IPH2101 Induces Contraction and Hyporesponsiveness of NK Cells in Patients with Myeloma.
Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers, 2 of them syntheses that pooled it.
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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
114 citing papers in PubMed, 2 syntheses or guidelines pooled it, 163 citations in OpenAlex.
- Evaluating early intervention in smoldering myeloma clinical trials: a systematic review.The oncologist · 2025Pooled it
- Emerging immune targets for the treatment of multiple myeloma.Immunotherapy · 2018Pooled it
- Autoantibodies to Killer Cell Immunoglobulin-Like Receptors in Patients With Systemic Lupus Erythematosus Induce Natural Killer Cell Hyporesponsiveness.Frontiers in immunology · 2019Trial
- Monocytes and Granulocytes Reduce CD38 Expression Levels on Myeloma Cells in Patients Treated with Daratumumab.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Trial
- Mechanisms of tumor cell evasion from NK cell-mediated killing and advances in NK cell-based cancer immunotherapy.Pharmaceutical science advances · 2026Review
- The dual roles of natural killer cells in liver immunity and tolerance: Implications for health and disease.Hepatology communications · 2026Review
- Structural mechanism of anti-MHC-I antibody blocking of inhibitory NK cell receptors in tumor immunity.Communications biology · 2026Article
- Article
- TNF-α and IFN-γ differentially regulate AML cell susceptibility to CD70-antibody-mediated cytotoxicity.Journal for immunotherapy of cancer · 2025Article
- Antibody-Mediated Inhibition of HLA/LILR Interactions Breaks Innate Immune Tolerance and Induces Antitumor Immunity.Cancer immunology research · 2025Article
- Pan-cancer NK cell-related immunotherapy signatures for predicting PD-1 treatment response.Medicine · 2025Article
- Structural mechanism of anti-MHC-I antibody blocking of inhibitory NK cell receptors in tumor immunity.Research square · 2025Article
- Unleashing NK cells for cancer immunotherapy in lung cancer: biologic challenges and clinical advances.Journal of experimental & clinical cancer research : CR · 2025Review
- Natural Killer Cell Immune Checkpoints and Their Therapeutic Targeting in Cancer Treatment.Research (Washington, D.C.) · 2025Article
- The Role of Natural Killer Cells in the Tumor Immune Microenvironment of EBV-Associated Nasopharyngeal Carcinoma.Cancers · 2024Review
- Innate Lymphoid Cells in Bladder Cancer: From Mechanisms of Action to Immune Therapies.Cancer immunology research · 2024Review
- Structural basis for the activity and specificity of the immune checkpoint inhibitor lirilumab.Scientific reports · 2024Article
- Multiple myeloma and the potential of new checkpoint inhibitors for immunotherapy.Therapeutic advances in vaccines and immunotherapy · 2024Review
- Advancements in microenvironment-based therapies: transforming the landscape of multiple myeloma treatment.Frontiers in oncology · 2024Review
- The basic biology of NK cells and its application in tumor immunotherapy.Frontiers in immunology · 2024Review
54 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
purposeImmune checkpoint inhibitors have recently revolutionized cancer immunotherapy. On the basis of data showing KIR-ligand mismatched natural killer (NK) cells reduce the risk of leukemia and multiple myeloma relapse following allogeneic hematopoietic stem cell transplantation, investigators have developed a checkpoint inhibition antibody that blocks KIR on NK cells. Although in vitro studies suggest the KIR2D-specific antibody IPH2101 induces KIR-ligand mismatched tumor killing by NK cells, our single-arm phase II clinical trial in patients with smoldering multiple myeloma was prematurely terminated due to lack of clinical efficacy. This study aimed at unveiling the underlying mechanisms behind the lack of clinical efficacy. EXPERIMENTAL
designTreatment-naïve patients received an intravenous infusion of 1 mg/kg IPH2101 every other month for up to a year. Peripheral blood was collected at baseline and 24 hours after first infusion, followed by weekly samples for the first month and monthly samples thereafter. NK cell phenotype and function was analyzed using high-resolution flow cytometry.
resultsUnexpectedly, infusion of IPH2101 resulted in rapid reduction in both NK cell responsiveness and KIR2D expression on the NK cell surface. In vitro assays revealed KIR2D molecules are removed from the surface of IPH2101-treated NK cells by trogocytosis, with reductions in NK cell function directly correlating with loss of free KIR2D surface molecules. Although IPH2101 marginally augmented the antimyeloma cytotoxicity of remaining KIR2D
conclusionsThese data raise concerns that the unexpected biological events reported in this study could compromise antibody-based strategies designed at augmenting NK cell tumor killing via checkpoint inhibition. Clin Cancer Res; 22(21); 5211-22. ©2016 AACRSee related commentary by Felices and Miller, p. 5161.
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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.