ArticleCancer cell2022
Non-cleavable hinge enhances avidity and expansion of CAR-T cells for acute myeloid leukemia.
Article in Cancer cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers, 2 of them syntheses that pooled it.
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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
100 citing papers in PubMed, 2 syntheses or guidelines pooled it, 132 citations in OpenAlex.
- Strategies and mechanisms for the enhancement of chimeric antigen receptor T-cell functions.Science China. Life sciences · 2026Pooled it
- Mapping the frontiers: a bibliometric perspective on t cell-based immunotherapy in pancreatic cancer since the twenty-first century.Journal of cancer research and clinical oncology · 2025Pooled it
- Multi-dimensional orchestration of binders for improved CAR-T immunotherapy.Cancer letters · 2026Review
- Mismatch Repair-Proficient Colorectal Cancer Can Evade Immune Surveillance through an Intrinsic Suppressive Program.Cancer discovery · 2026Article
- Pediatric AML CAR T cell therapy.Molecular therapy. Oncology · 2026Review
- Review
- Enhancing iNKT cell immunotherapy through the integration of optimized CAR endodomains and iNKT engagers.Nature communications · 2026Article
- A guide to CAR T cell therapies: development, current status and future prospects.Nature reviews. Immunology · 2026Review
- Enhancing persistence while managing cytokine release syndrome to embrace next-generation CAR-T cell therapy.Journal of translational medicine · 2026Review
- Bispecific CD37-Siglec6 CAR‑T cells exhibit enhanced anti‑leukemic activity and reduced exhaustion in acute myeloid leukemia xenograft models.Journal of translational medicine · 2026Article
- IDR-induced CAR condensation improves the cytotoxicity of CAR-Ts against low-antigen cancers.Nature chemical biology · 2026Article
- Synthetic cleavage-resistant TREM2 boosts macrophage efferocytosis to treat inflammatory diseases.Cell reports. Medicine · 2026Article
- Next-generation CAR-T therapy for acute myeloid leukemia: bridging innovation with clinical translation.Annals of hematology · 2026Review
- Article
- TIGIT disruption rescues the antitumor activity of low avidity TCR-engineered T cells by increasing TCR signal strength.Nature communications · 2026Article
- Immunotherapy for Leiomyosarcoma: Current Status and Perspectives.Journal of immunology research · 2026Review
- Affinity-matured CD72-targeting nanobody CAR T cells enhance elimination of antigen-low B-cell malignancies.Journal for immunotherapy of cancer · 2025Article
- International consensus guidelines for the conduct and reporting of CAR T-cell clinical trials in AML.Blood advances · 2025Article
- Targeting leukemic stem cell biomechanics suppresses stemness and enhances NK cell-mediated immunotherapy.Nature communications · 2025Article
- T-Cell Responses and T-Cell-Based Therapy in Acute Myeloid Leukemia.Current medical science · 2025Review
40 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
Chimeric antigen receptor (CAR) T cell therapy is effective in lymphoid malignancies, but there has been limited data in myeloid cancers. Here, we start with a CD27-based CAR to target CD70 ("native") in acute myeloid leukemia (AML), and we find modest efficacy in vivo, consistent with prior reports. We then use orthogonal approaches to increase binding on both the tumor and CAR-T cell sides of the immune synapse: a pharmacologic approach (azacitidine) to increase antigen density of CD70 in myeloid tumors, and an engineering approach to stabilize binding of the CAR to CD70. To accomplish the latter, we design a panel of hinge-modified regions to mitigate cleavage of the extracellular portion of CD27. Our CD8 hinge and transmembrane-modified CD70 CAR-T cells are less prone to cleavage, have enhanced binding avidity, and increased expansion, leading to more potent in vivo activity. This enhanced CD70-targeted CAR is a promising candidate for further clinical development.
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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.