ArticleJournal for immunotherapy of cancer2021
Peptide: MHC-based DNA vaccination strategy to activate natural killer cells by targeting killer cell immunoglobulin-like receptors.
Article in Journal for immunotherapy of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- The Role of Killer Ig-like Receptors in Diseases from A to Z.International journal of molecular sciences · 2025Review
- Post-translational modification of NK cell receptors offers clues to antigenic specificity riddle.Frontiers in immunology · 2025Review
- Peptide-specific natural killer cell receptors.Oxford open immunology · 2025Review
- The nuclear export protein XPO1 provides a peptide ligand for natural killer cells.Science advances · 2024Article
- Beyond CAR-T: The rise of CAR-NK cell therapy in asthma immunotherapy.Journal of translational medicine · 2024Review
- KIR2DS2+ NK cells in cancer patients demonstrate high activation in response to tumour-targeting antibodies.Frontiers in oncology · 2024Article
- Targeting KIR as a novel approach to improve CAR-NK cell function.Journal of translational genetics and genomics · 2023Article
- Peptide Hydrogels as Immunomaterials and Their Use in Cancer Immunotherapy Delivery.Advanced healthcare materials · 2023Review
- KIR2DS2 Expression Identifies NK Cells With Enhanced Anticancer Activity.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Peanut oral immunotherapy: current trends in clinical trials.Immunotherapy advances · 2022Review
- Natural Killer Cells and Type 1 Innate Lymphoid Cells in Hepatocellular Carcinoma: Current Knowledge and Future Perspectives.International journal of molecular sciences · 2021Review
- Relevance of Polymorphic KIR and HLA Class I Genes in NK-Cell-Based Immunotherapies for Adult Leukemic Patients.Cancers · 2021Review
- Combination of Ablation and Immunotherapy for Hepatocellular Carcinoma: Where We Are and Where to Go.Frontiers in immunology · 2021Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundNatural killer (NK) cells are increasingly being recognized as agents for cancer immunotherapy. The killer cell immunoglobulin-like receptors (KIRs) are expressed by NK cells and are immunogenetic determinants of the outcome of cancer. In particular, KIR2DS2 is associated with protective responses to several cancers and also direct recognition of cancer targets in vitro. Due to the high homology between activating and inhibitory KIR genes to date, it has been challenging to target individual KIR for therapeutic benefit.
methodsA novel KIR2DS2-targeting therapeutic peptide:MHC DNA vaccine was designed and used to immunize mice transgenic for KIR genes (KIR-Tg). NK cells were isolated from the livers and spleens of vaccinated mice and then analyzed for activation by flow cytometry, RNA profiling and cytotoxicity assays. In vivo assays of NK cell function using a syngeneic cancer model (B16 melanoma) and an adoptive transfer model for human hepatocellular carcinoma (Huh7) were performed.
resultsInjecting KIR-Tg mice with the vaccine construct activated NK cells in both liver and spleens of mice, with preferential activation of KIR2DS2-positive NK cells. KIR-specific activation was most marked on the CD11b+CD27+ mature subset of NK cells. RNA profiling indicated that the DNA vaccine upregulated genes associated with cellular metabolism and downregulated genes related to histone H3 methylation, which are associated with immune cell maturation and NK cell function. Vaccination led to canonical and cross-reactive peptide:MHC-specific NK cell responses. In vivo, DNA vaccination led to enhanced antitumor responses against B16F10 melanoma cells and also enhanced responses against a tumor model expressing the KIR2DS2 ligand HLA-C*0102.
conclusionWe show the feasibility of a peptide-based KIR-targeting vaccine strategy to activate NK cells and hence generate functional antitumor responses. This approach does not require detailed knowledge of the tumor peptidomes nor HLA matching with the patient. It therefore offers a novel opportunity for targeting NK cells for cancer immunotherapy.
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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.