ArticleMolecular therapy : the journal of the American Society of Gene Therapy2022
Targeting HLA-DR loss in hematologic malignancies with an inhibitory chimeric antigen receptor.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 33 citations in OpenAlex.
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- Next-generation CAR-T therapy for acute myeloid leukemia: bridging innovation with clinical translation.Annals of hematology · 2026Review
- From monoclonals to bispecific T cell engagers: the evolving antibody-based therapy landscape in acute myeloid leukemia.Frontiers in immunology · 2026Review
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- CAR-NK cell therapy in multiple myeloma: from preclinical and clinical landscape to joining the force for treatment strategies optimization.Cell communication and signaling : CCS · 2025Review
- CAR NK cell therapy for solid tumors: potential and challenges.Antibody therapeutics · 2025Review
- Strategic innovations: Tackling challenges of immunotherapy in acute myeloid leukemia.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2025Article
- Mesenchymal stem cells in treating human diseases: molecular mechanisms and clinical studies.Signal transduction and targeted therapy · 2025Review
- Causal relationship among immune cells, basal cell carcinoma, and gut microbiome: a two-sample Mendelian randomization analysis and mediation analysis.Discover oncology · 2025Article
- NK cells in HPV-related tumorigenesis: mechanisms and clinical applications.Frontiers in cellular and infection microbiology · 2025Review
- NK cell-based immunotherapy strategies for myeloid leukemia.Frontiers in immunology · 2025Review
- Assessing the causal relationship between circulating immune cells and abdominal aortic aneurysm by bi-directional Mendelian randomization analysis.Scientific reports · 2024Article
- Article
- Revolutionizing Immunotherapy: Unveiling New Horizons, Confronting Challenges, and Navigating Therapeutic Frontiers in CAR-T Cell-Based Gene Therapies.ImmunoTargets and therapy · 2024Review
- The Importance of Confirming False Homozygosity in Pretransplant HLA Typing Results of Patients with Hematologic Malignancies.International journal of medical sciences · 2024Article
- Decoding the prognostic landscape of LUAD: the interplay between NFrontiers in immunology · 2024Article
- Influencing factors and solution strategies of chimeric antigen receptor T-cell therapy (CAR-T) cell immunotherapy.Oncology research · 2024Review
- Dual-inhibitory domain iCARs improve the efficiency of the AND-NOT gate CAR T strategy.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Tuning CARs: recent advances in modulating chimeric antigen receptor (CAR) T cell activity for improved safety, efficacy, and flexibility.Journal of translational medicine · 2023Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Chimeric antigen receptor natural killer (CAR-NK) cells have remarkable cytotoxicity against hematologic malignancies; however, they may also attack normal cells sharing the target antigen. Since human leukocyte antigen DR (HLA-DR) is reportedly lost or downregulated in a substantial proportion of hematologic malignancies, presumably a mechanism to escape immune surveillance, we hypothesize that the anti-cancer specificity of CAR-NK cells can be enhanced by activating them against cancer antigens while inhibiting them against HLA-DR. Here, we report the development of an anti-HLA-DR inhibitory CAR (iCAR) that can effectively suppress NK cell activation against HLA-DR-expressing cells. We show that dual CAR-NK cells, which co-express the anti-CD19 or CD33 activating CAR and the anti-HLA-DR iCAR, can preferentially target HLA-DR-negative cells over HLA-DR-positive cells in vitro. We find that the HLA-DR-mediated inhibition is positively correlated with both iCAR and HLA-DR densities. We also find that HLA-DR-expressing surrounding cells do not affect the target selectivity of dual CAR-NK cells. Finally, we confirm that HLA-DR-positive cells are resistant to dual CAR-NK cell-mediated killing in a xenograft mouse model. Our approach holds great promise for enhancing CAR-NK and CAR-T cell specificity against malignancies with HLA-DR loss.
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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.