ArticleMolecular therapy : the journal of the American Society of Gene Therapy2021
Engineering Tolerance toward Allogeneic CAR-T Cells by Regulation of MHC Surface Expression with Human Herpes Virus-8 Proteins.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- Next-generation CAR-T therapy for acute myeloid leukemia: bridging innovation with clinical translation.Annals of hematology · 2026Review
- Mesenchymal Stromal Cells: Bridging the Gaps in Hematologic Disease Therapy.Stem cell reviews and reports · 2026Review
- Harnessing the potential of gene editing technology for CAR-T cell therapy of solid tumors.Inflammation and regeneration · 2025Review
- Fine tuning towards the next generation of engineered T cells.Nature biomedical engineering · 2025Review
- Dysfunction of natural killer cells promotes immune escape and disease progression in endometriosis.Frontiers in immunology · 2025Review
- Advancements in adoptive CAR immune cell immunotherapy synergistically combined with multimodal approaches for tumor treatment.Bioactive materials · 2024Review
- Protein ubiquitination in ovarian cancer immunotherapy: The progress and therapeutic strategy.Genes & diseases · 2024Review
- Engineering immune-evasive allogeneic cellular immunotherapies.Nature reviews. Immunology · 2024Review
- Leveraging oncovirus-derived antigen against the viral malignancies in adoptive cell therapies.Biomarker research · 2024Review
- NOT gated T cells that selectively target EGFR and other widely expressed tumor antigens.iScience · 2024Article
- Current approaches to develop "off-the-shelf" chimeric antigen receptor (CAR)-T cells for cancer treatment: a systematic review.Experimental hematology & oncology · 2023Review
- Harnessing novel strategies and cell types to overcome immune tolerance during adoptive cell therapy in cancer.Journal for immunotherapy of cancer · 2023Review
- Endowing universal CAR T-cell with immune-evasive properties using TALEN-gene editing.Nature communications · 2022Article
- Reprogramming the tumor microenvironment by genome editing for precision cancer therapy.Molecular cancer · 2022Review
- Incorporation of bacterial immunoevasins to protect cell therapies from host antibody-mediated immune rejection.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Current Perspectives on the Use of off the Shelf CAR-T/NK Cells for the Treatment of Cancer.Cancers · 2021Review
- Off-the-Shelf Chimeric Antigen Receptor T Cells: How Do We Get There?Cancer journal (Sudbury, Mass.)Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Allogeneic, off-the-shelf (OTS) chimeric antigen receptor (CAR) cell therapies have the potential to reduce manufacturing costs and variability while providing broader accessibility to cancer patients and those with other diseases. However, host-versus-graft reactivity can limit the durability and efficacy of OTS cell therapies requiring new strategies to evade adaptive and innate-immune responses. Human herpes virus-8 (HHV8) maintains infection, in part, by evading host T and natural killer (NK) cell attack. The viral K3 gene encodes a membrane-tethered E3 ubiquitin ligase that discretely targets major histocompatibility complex (MHC) class I components, whereas K5 encodes a similar E3 ligase with broader specificity, including MHC-II and the MHC-like MHC class I polypeptide-related sequence A (MIC-A)- and sequence B (MIC-B)-activating ligands of NK cells. We created γ-retroviruses encoding K3 and/or K5 transgenes that efficiently transduce primary human T cells. Expression of K3 or K5 resulted in dramatic downregulation of MHC-IA (human leukocyte antigen [HLA]-A, -B, and -C) and MHC class II (HLA-DR) cell-surface expression. K3 expression was sufficient for T cells to resist exogenously loaded peptide-MHC-specific cytotoxicity, as well as recognition in one-way allogeneic mixed lymphocyte reactions. Further, in immunodeficient mice engrafted with allogeneic T cells, K3-transduced T cells selectively expanded in vivo. Ectopic K5 expression in MHC class I
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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.