ArticleJournal of hematology & oncology2025
First-in-human evaluation of memory-like NK cells with an IL-15 super-agonist and CTLA-4 blockade in advanced head and neck cancer.
Article in Journal of hematology & oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04290546 (A Phase 1 Trial of CTLA-4 Inhibition, With or Without Cetuximab, and in Combination With Memory-like Natural Killer), which is not on this map. Cited by 26 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
A Phase 1 Trial of CTLA-4 Inhibition, With or Without Cetuximab, and in Combination With Memory-like Natural Killer (NK) Cell Immune Cell Therapy in Advanced Head & Neck Cancer
Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it.
- NK cell adoptive transfer in acute myeloid leukemia: a systematic review and meta-analysis.Frontiers in immunology · 2026Pooled it
- IL-15 trans-presentation at the innate-adaptive interface: mechanisms and translation in cancer immunotherapy.Oncoimmunology · 2026Review
- Mechanisms of tumor cell evasion from NK cell-mediated killing and advances in NK cell-based cancer immunotherapy.Pharmaceutical science advances · 2026Review
- The CREM-IL-15 axis: decoding the persistence-exhaustion paradox in NK cell immunotherapy.Cancer immunology, immunotherapy : CII · 2026Review
- Advancing CAR-NK cell therapy in solid tumors: Current landscape and future directions.Cell reports. Medicine · 2026Review
- Natural Killer Cell Immunotherapy in Solid Tumors: Microenvironmental Obstacles and Translational 3D Models.Biology · 2026Review
- Circumventing Ewing sarcoma tumor microenvironment resistance by IL1RAP CAR-modified TGFβ1-imprinted natural killer cells in combination with IL-15 agonist and anti-GD2 antibody.Journal for immunotherapy of cancer · 2026Article
- Cellular immunotherapy in melanoma: the next frontier in cancer treatment.Journal of experimental & clinical cancer research : CR · 2026Review
- Review
- Tumor microenvironment-driven natural killer cell diversity: mechanisms and therapeutic opportunities.Cancer biology & medicine · 2026Review
- Current development and challenges of NK cell-based immunotherapy for gastrointestinal cancers.International journal of clinical oncology · 2026Review
- Altered natural killer cell function in children with severe malaria.ImmunoHorizons · 2026Article
- Parallel processing of T cells and natural killer cells to enhanceClinical & translational immunology · 2026Article
- Automated manufacturing of clinical-grade BDCA2 CAR NK cells in a closed system for the treatment of blastic plasmacytoid dendritic cell neoplasm.Frontiers in immunology · 2026Article
- A novel cultivation strategy to recover NK cell cytotoxicity.Frontiers in bioengineering and biotechnology · 2026Article
- A new era of natural killer cell immunotherapy in tumor treatment: latest advances and cutting-edge perspectives from basic research to clinical practice.Frontiers in immunology · 2026Review
- TIME for Endometrial Cancer: Advancements and Challenges in Therapeutic Targets for the Endometrial Cancer Tumor Immune Microenvironment.Cancer immunology research · 2025Review
- Site-specific genome engineering of primary human natural killer cells for programmable anti-tumor function.bioRxiv : the preprint server for biology · 2025Article
- Review
- Natural Killer Cell-Mediated Antitumor Immunity: Molecular Mechanisms and Clinical Applications.MedComm · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
28 authors.
Funding
Abstract
backgroundCytokine induced memory-like natural killer (CIML NK) cells combined with an IL-15 super-agonist (N-803) are a novel modality to treat relapsed/refractory head and neck cancer.
methodsWe report data from a phase I trial of haploidentical CIML NK cells combined with N-803 with or without ipilimumab (IPI) in relapsed/refractory head and neck cancer patients after a median of 6 prior lines of therapy. The trial adhered to a 3 + 3 dose de-escalation design, with primary endpoint being safety. High-resolution immunophenotypic and transcriptional profiling characterized the NK cells and their interacting partners in vivo.
resultsThe primary safety endpoint was established, with dose-limiting toxicity in 1/10 patients. A transient disease control rate correlated with donor NK cell expansion, the latter occurring irrespective of IPI. The combination of CIML NK cells with N-803 and IPI was associated with increased early NK cell proliferation, contraction of Treg: Tcon, rapid recovery of recipient CD8
conclusionsCIML NK cells combined with N-803 and ipilimumab to treat head and neck cancer is safe, and associated with a more proliferative NK cell phenotype. However, the combination leads to reduced HLA mismatched NK cell persistence, resulting in an important limitation affecting NK cell combination therapies in clinical trials. These results inform evaluation of CIML NK therapy for advanced malignancies, with considerations for combination with IPI.
trial registrationNCT04290546.
Indexed as
Identifiers
What OpenQuestion holds
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.