ArticleThe Journal of clinical investigation2016
CD62L+ NKT cells have prolonged persistence and antitumor activity in vivo.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 papers.
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Who cites it
119 citing papers in PubMed, 171 citations in OpenAlex.
- Cultivating Functional Natural Killer Cells from Mobilized Hematopoietic Stem Cells in Heavily Pretreated Hematologic Malignancies.International journal of molecular sciences · 2026Article
- Natural Killer T Cell Function in Lymphoma Patients.Biomolecules · 2026Article
- IL-18 metabolically reprograms CAR-expressing natural killer T cells and enhances their antitumor activity.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Expression of CD38 on resting peripheral iNKT cells defines an immature subpopulation with distinct functionality in humans.Immunology and cell biology · 2026Article
- Article
- Metabolic control of innate-like T cells.Nature reviews. Immunology · 2026Review
- Facts and Hopes of Chimeric Antigen Receptor-Redirected NK T Cells.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Review
- Genome-edited allogeneic CAR-T cells: the next generation of cancer immunotherapies.Journal of hematology & oncology · 2025Review
- Dual regulatory role of natural killer T cells during development of hepatocellular carcinoma.Communications biology · 2025Article
- Engineering adoptive cell therapy for solid tumors.Medical oncology (Northwood, London, England) · 2025Review
- Expanding Immunotherapy Beyond CAR T Cells: Engineering Diverse Immune Cells to Target Solid Tumors.Cancers · 2025Review
- Single-cell transcriptomics uncovers key immune drivers of vaccine efficacy in cattle.BMC genomics · 2025Article
- Advancing CAR-based cell therapies for solid tumours: challenges, therapeutic strategies, and perspectives.Molecular cancer · 2025Review
- The landscape of CAR-engineered innate immune cells for cancer immunotherapy.Nature cancer · 2025Review
- Single-cell transcriptomic profiling reveals diversity in human iNKT cells across hematologic tissues.Cell reports · 2025Article
- PRDM1 Is a Key Regulator of the NKT-cell Central Memory Program and Effector Function.Cancer immunology research · 2025Article
- Hyperleukocytosis in a neuroblastoma patient after treatment with natural killer T cells expressing a GD2-specific chimeric antigen receptor and IL-15.Journal for immunotherapy of cancer · 2025Article
- CAR-iNKT cells: redefining the frontiers of cellular immunotherapy.Frontiers in immunology · 2025Review
- Innate iNKT cells: from biological insight to clinical impact.Frontiers in immunology · 2025Review
- Cord blood-derived iNK T cells as a platform for allogeneic CAR T cell therapy.Frontiers in immunology · 2025Article
59 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Vα24-invariant natural killer T cells (NKTs) localize to tumors and have inherent antitumor properties, making them attractive chimeric antigen receptor (CAR) carriers for redirected cancer immunotherapy. However, clinical application of CAR-NKTs has been impeded, as mechanisms responsible for NKT expansion and the in vivo persistence of these cells are unknown. Here, we demonstrated that antigen-induced expansion of primary NKTs in vitro associates with the accumulation of a CD62L+ subset and exhaustion of CD62L- cells. Only CD62L+ NKTs survived and proliferated in response to secondary stimulation. When transferred to immune-deficient NSG mice, CD62L+ NKTs persisted 5 times longer than CD62L- NKTs. Moreover, CD62L+ cells transduced with a CD19-specific CAR achieved sustained tumor regression in a B cell lymphoma model. Proliferating CD62L+ cells downregulated or maintained CD62L expression when activated via T cell receptor alone or in combination with costimulatory receptors. We generated HLAnull K562 cell clones that were engineered to express CD1d and costimulatory ligands. Clone B-8-2 (HLAnullCD1dmedCD86high4-1BBLmedOX40Lhigh) induced the highest rates of NKT expansion and CD62L expression. B-8-2-expanded CAR-NKTs exhibited prolonged in vivo persistence and superior therapeutic activities in models of lymphoma and neuroblastoma. Therefore, we have identified CD62L as a marker of a distinct NKT subset endowed with high proliferative potential and have developed artificial antigen-presenting cells that generate CD62L-enriched NKTs for effective cancer immunotherapy.
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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.