ArticleClinical cancer research : an official journal of the American Association for Cancer Research2023
Memory-like Differentiation, Tumor-Targeting mAbs, and Chimeric Antigen Receptors Enhance Natural Killer Cell Responses to Head and Neck Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 21 citations in OpenAlex.
- NK cell dysregulation may potentiate cardiovascular disease in adolescents with perinatally acquired HIV on antiretroviral therapy.Nature communications · 2026Article
- Beyond αβ T cells: unlocking the potential of diverse immune cells in CAR modification.Clinical science (London, England : 1979) · 2026Review
- Enhancing CAR-NK persistence to unlock its full therapeutic potentials.Frontiers in immunology · 2026Review
- Therapeutic reprogramming of natural killer cells for solid tumors: expanding frontiers into rare and ultra-rare malignancies.Frontiers in molecular biosciences · 2026Review
- Anti-MSLN chimeric antigen receptor-like NK cell therapy with tumor-penetrating capacity (uCAR-like NK) for solid tumors.Signal transduction and targeted therapy · 2025Article
- Interferon signaling and STING pathway in head and neck cancers: unlocking immune secrets and therapeutic frontiers.Cancer cell international · 2025Review
- EGFR: New Insights on Its Activation and Mutation in Tumor and Tumor Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Tumor hypoxia shapes natural killer cell anticancer activities.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Engineering innate immune cells for cancer immunotherapy.Nature biotechnology · 2025Review
- Preclinical investigation of anti-tumor efficacy of allogeneic natural killer cells combined with cetuximab for head and neck squamous cell carcinoma.Cancer immunology, immunotherapy : CII · 2025Article
- 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.Journal of hematology & oncology · 2025Article
- CD56Journal for immunotherapy of cancer · 2025Article
- Memory-like NK cell differentiation, inhibitory NKG2A blockade, and improved recognition via antibody or CAR engineering combine to enhance NK cell attack against multiple myeloma.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Enhancement of anti-sarcoma immunity by NK cells engineered with mRNA for expression of a EphA2-targeted CAR.Clinical and translational medicine · 2025Article
- Natural killer cell memory: challenges and opportunities for cancer immunotherapy.Cancer biology & therapy · 2024Review
- CAR memory-like NK cells targeting the membrane proximal domain of mesothelin demonstrate promising activity in ovarian cancer.Science advances · 2024Article
- Bridging the gap with multispecific immune cell engagers in cancer and infectious diseases.Cellular & molecular immunology · 2024Review
- Harnessing natural killer cell effector function against cancer.Immunotherapy advances · 2024Review
- Natural killer cells: a future star for immunotherapy of head and neck squamous cell carcinoma.Frontiers in immunology · 2024Review
- NK cell based immunotherapy against oral squamous cell carcinoma.Frontiers in immunology · 2024Review
Corrections and comments
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Authors and funding
27 authors at 2 institutions in 1 country.
Funding
Abstract
purposeHead and neck squamous cell carcinoma (HNSCC) is an aggressive tumor with low response rates to frontline PD-1 blockade. Natural killer (NK) cells are a promising cellular therapy for T cell therapy-refractory cancers, but are frequently dysfunctional in patients with HNSCC. Strategies are needed to enhance NK cell responses against HNSCC. We hypothesized that memory-like (ML) NK cell differentiation, tumor targeting with cetuximab, and engineering with an anti-EphA2 (Erythropoietin-producing hepatocellular receptor A2) chimeric antigen receptor (CAR) enhance NK cell responses against HNSCC. EXPERIMENTAL
designWe generated ML NK and conventional (c)NK cells from healthy donors, then evaluated their ability to produce IFNγ, TNF, degranulate, and kill HNSCC cell lines and primary HNSCC cells, alone or in combination with cetuximab, in vitro and in vivo using xenograft models. ML and cNK cells were engineered to express anti-EphA2 CAR-CD8A-41BB-CD3z, and functional responses were assessed in vitro against HNSCC cell lines and primary HNSCC tumor cells.
resultsHuman ML NK cells displayed enhanced IFNγ and TNF production and both short- and long-term killing of HNSCC cell lines and primary targets, compared with cNK cells. These enhanced responses were further improved by cetuximab. Compared with controls, ML NK cells expressing anti-EphA2 CAR had increased IFNγ and cytotoxicity in response to EphA2+ cell lines and primary HNSCC targets.
conclusionsThese preclinical findings demonstrate that ML differentiation alone or coupled with either cetuximab-directed targeting or EphA2 CAR engineering were effective against HNSCCs and provide the rationale for investigating these combination approaches in early phase clinical trials for patients with HNSCC.
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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.