ArticleCancer immunology, immunotherapy : CII2025
NKG2D CAR-NK adoptive cellular immunotherapy combined with or without PD-1 blockade in the treatment of patients with metastatic colorectal cancer: an exploratory study.
Article in Cancer immunology, immunotherapy : CII, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05213195 (NKG2D CAR-NK Cell Therapy in Patients With Refractory Metastatic Colorectal Cancer), which is not on this map. Cited by 12 papers.
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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.
NKG2D CAR-NK Cell Therapy in Patients With Refractory Metastatic Colorectal Cancer
Who cites it
12 citing papers in PubMed.
- Colorectal Cancer: Epidemiology, Risk Factors, Signaling Pathways, Clinical Features, Screening, Diagnosis, and Management.MedComm · 2026Review
- Barriers and Blueprints: Next-Generation Engineering Strategies for CAR-T Cell Therapy in Gastrointestinal Tumors.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Safety and feasibility of 5T4 antibody-coupled allogeneic NK cell therapy for solid tumors: a first-in-human phase 1 trial.Cancer immunology, immunotherapy : CII · 2026Article
- Beyond CAR-T and oncology: broadening chimeric antigen receptor technologies across cell types and diseases.Precision clinical medicine · 2026Review
- Interplay between natural killer cells and ferroptosis: novel insights in tumor immunity and therapeutic potential.Cell communication and signaling : CCS · 2026Review
- Combined carbon ion radiotherapy and immunotherapy: leveraging the immunological advantages of carbon ion.Frontiers in immunology · 2026Review
- Engineering with EP2/EP4 knockout and IL-15 transpresentation renders stem cell-derived NK cells self-persistent and resistant to PGE2 inhibition.Frontiers in immunology · 2026Article
- CEA-targeted CAR-NK cells derived from embryonic stem cells exhibit potent anti-tumor activity against colorectal cancer.Frontiers in immunology · 2026Article
- Enhancing CAR-NK persistence to unlock its full therapeutic potentials.Frontiers in immunology · 2026Review
- Review
- Advances in chimeric antigen receptor-natural killer cell therapy: from mechanisms and preclinical studies to clinical application.Frontiers in oncology · 2025Review
- Engineering immunity with CAR-NK cells: advancing the frontiers of cancer immunotherapy.Frontiers in pharmacology · 2025Review
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
backgroundColorectal cancer (CRC) remains a leading cause of cancer-related death worldwide, with limited treatment options for patients with metastatic disease. Chimeric antigen receptor (CAR)-engineered natural killer (NK) cells represent a novel immunotherapeutic approach with potential advantages in safety and allogeneic applicability.
methodsThis is a multi-arm phase I clinical trial (NCT05213195) evaluating the safety and feasibility of NKG2D-based CAR-NK cells expressing membrane-bound IL-15 (mbIL-15) in advanced CRC. Here, we report the results from the cohort expansion stage of this trial. Totally, six heavily pretreated patients were enrolled and received lymphodepletion chemotherapy followed by four infusions of CAR-NK cells in 2 weeks. Two cohorts were designed to assess extended infusion routes and combination with anti-PD-1 antibodies.
resultsCAR-NK therapy was well tolerated, with no treatment-related death or serious non-hematologic toxicities. Common adverse events included reversible cytokine-release syndrome (CRS) and mild gastrointestinal symptoms. Notably, potential clinical benefits were observed in patients who received CAR-NK cells in combination with anti-PD-1 therapy, including one patient who achieved stable disease (SD) and two others who experienced prolonged overall survival exceeding 700 days, suggesting a potential synergistic effect. Meanwhile, CAR-NK cells were detectable in peripheral blood within two weeks after infusion. And the combination with PD-1 blockade was associated with substantially increased peak CAR transgene levels compared to monotherapy (median CAR copies, 45,593 versus 1001).
conclusionNKG2D CAR-NK cell therapy, alone or combined with PD-1 blockade, demonstrated a favorable safety profile and potential clinical benefit in advanced CRC, warranting further investigation in larger cohorts.
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Registered trials
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