ArticleNature medicine2022
HLA-independent T cell receptors for targeting tumors with low antigen density.
Article in Nature medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 139 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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.
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Who cites it
139 citing papers in PubMed, 1 synthesis or guideline pooled it, 175 citations in OpenAlex.
- Role of CD19 Chimeric Antigen Receptor T Cells in Second-Line Large B Cell Lymphoma: Lessons from Phase 3 Trials. An Expert Panel Opinion from the American Society for Transplantation and Cellular Therapy.Transplantation and cellular therapy · 2022Guideline
- Cancers modulate processing and presentation of p53 neoantigens to evade T cell detection.Immunity · 2026Article
- CRISPRa screen unveils noncanonical NF-κB to boost the antitumor activity of TCR-based CAR-T cells.Cellular & molecular immunology · 2026Article
- Engineered CTLA-4 targeting chimeras for targeted protein degradation and immune synapse reprogramming.bioRxiv : the preprint server for biology · 2026Article
- Computational design of optimized and preferentially paired human TCR constant regions for improved T cell function.Science advances · 2026Article
- Chimeric antigen receptor (CAR)-T cell therapy for solid tumors in pediatric patients: current breakthroughs, dilemmas, and strategies.Experimental hematology & oncology · 2026Review
- A guide to CAR T cell therapies: development, current status and future prospects.Nature reviews. Immunology · 2026Review
- Humanized biparatopic nanobody-based CAR-T cells overcome antigen-heterogeneity in multiple myeloma.Journal of translational medicine · 2026Article
- Regulatory challenges of personalized medicine in the real world: are the right patients being treated with CD19-targeting CAR T-cells?EMBO molecular medicine · 2026Review
- Review
- Generation of therapeutic T cells from human induced pluripotent stem cells.Inflammation and regeneration · 2026Review
- Challenges and advances in CAR-T cell therapy for B-ALL.Biomarker research · 2026Review
- Balancing the efficacy and safety of chimeric antigen receptor T-cell therapy by affinity combination.Nature communications · 2026Article
- Roads and detours for CAR T cell therapy in autoimmune diseases.Nature reviews. Drug discovery · 2026Review
- Targeting endosomal trafficking-mediated antigen escape to resensitize myeloma to CAR-T therapy.Journal for immunotherapy of cancer · 2026Article
- A CD22-specific T-cell receptor enables effective adoptive T-cell therapy for B-cell malignancies.Blood · 2026Article
- IDR-induced CAR condensation improves the cytotoxicity of CAR-Ts against low-antigen cancers.Nature chemical biology · 2026Article
- Article
- Sensitive CAR T cells redefine targetable CD70 expression in solid tumors.Science (New York, N.Y.) · 2026Article
- Targeting epigenetic regulators to boost T cell immunotherapy against cancer.Cell & bioscience · 2026Review
79 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
25 authors at 4 institutions in 4 countries.
Funding
Abstract
Chimeric antigen receptors (CARs) are receptors for antigen that direct potent immune responses. Tumor escape associated with low target antigen expression is emerging as one potential limitation of their efficacy. Here we edit the TRAC locus in human peripheral blood T cells to engage cell-surface targets through their T cell receptor-CD3 complex reconfigured to utilize the same immunoglobulin heavy and light chains as a matched CAR. We demonstrate that these HLA-independent T cell receptors (HIT receptors) consistently afford high antigen sensitivity and mediate tumor recognition beyond what CD28-based CARs, the most sensitive design to date, can provide. We demonstrate that the functional persistence of HIT T cells can be augmented by constitutive coexpression of CD80 and 4-1BBL. Finally, we validate the increased antigen sensitivity afforded by HIT receptors in xenograft mouse models of B cell leukemia and acute myeloid leukemia, targeting CD19 and CD70, respectively. Overall, HIT receptors are well suited for targeting cell surface antigens of low abundance.
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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.