ArticleScience immunology2024
CD5 deletion enhances the antitumor activity of adoptive T cell therapies.
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Article in Science immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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35citing papers in PubMed
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Who cites it
35 citing papers in PubMed.
- Risk Factors for Cardiovascular Disease: Epidemiology, Screening, Prevention, and Therapeutic Interventions.MedComm · 2026Review
- A guide to CAR T cell therapies: development, current status and future prospects.Nature reviews. Immunology · 2026Review
- In Vivo T-Cell Engineering: Revolution in Delivery Strategies and Clinical Translation.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- CCR4 expression defines a targetable subset of T-cell acute lymphoblastic leukemia.Blood advances · 2026Article
- Generation of T cells with reduced off-target cross-reactivities by engineering co-signalling receptors.Nature biomedical engineering · 2026Article
- Antigen-binding affinity is a key determinant of the durable antitumor activity of CD5 CAR-T cells.Molecular therapy. Oncology · 2026Article
- Efficacy and safety of autologous CD5-KO anti-CD5 CAR-T cells in relapsed/refractory CD5Cell reports. Medicine · 2026Article
- Single-Cell Dissection Reveals Immune Dysregulation After CD5 or CD7-Directed Chimeric Antigen Receptor T-Cell Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Advances in scCUT&Tag and computational analysis for single-cell gene regulatory element mapping.Briefings in bioinformatics · 2026Review
- TMEM33 deletion potentiates anti-tumor CD8bioRxiv : the preprint server for biology · 2026Article
- Rewriting CAR-T cell fate: CRISPR/Cas gene editing for solid tumor therapy.Frontiers in immunology · 2026Review
- The future directions of CAR-T Cell therapy: unlocking the potential of immunotherapy in cancer treatment.Frontiers in molecular medicine · 2026Review
- Histone methyltransferase DOT1L maintains cell state and restricts cytotoxic potential of CD8 T cells.Science advances · 2025Article
- Improving CAR T cell therapy against malignancies through gene knock-down/out strategies: a systematic review.Cancer cell international · 2025Review
- Next-generation T cell immunotherapies engineered with CRISPR base and prime editing: challenges and opportunities.Nature reviews. Clinical oncology · 2025Review
- Manufacturing of CRISPR-edited primary mouse CAR T cells for cancer immunotherapy.Nature protocols · 2025Article
- The multiple functions of CD5 in diseases related to immune disorders.Annals of medicine · 2025Review
- CD5 ablation enhances persistence and antitumor potency of engineered T cells by mitigating exhaustion and promoting cytotoxicity.Journal for immunotherapy of cancer · 2025Article
- Personalized Immunotherapy for T Cell Lymphomas: From Immune Escape to Precision Therapeutics.Journal of personalized medicine · 2025Review
- Review
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Authors and funding
51 authors.
Ruchi P PatelCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0001-8366-1928
Guido GhilardiCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-0095-3579
Yunlin ZhangCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-5608-0615
Yi-Hao ChiangCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0009-0005-8170-8629
Wei XieCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-4358-3950
Puneeth GuruprasadCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.
Ki Hyun KimCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0001-8835-7511
Inkook ChunCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.
Mathew G AngelosCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-9903-5021
Raymone PajarilloCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0003-3299-0929
Seok Jae HongCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0001-5360-8800
Yong Gu LeeCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0001-8099-628X
Olga ShestovaCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.
Carolyn ShawCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.
Ivan CohenCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.
Aasha GuptaCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.
Trang VuviTToria Biotherapeutics, Philadelphia, PA, USA.ORCID 0000-0002-8295-0450
Dean QianviTToria Biotherapeutics, Philadelphia, PA, USA.
Steven YangviTToria Biotherapeutics, Philadelphia, PA, USA.
Aditya NimmagaddaviTToria Biotherapeutics, Philadelphia, PA, USA.
Adam E SnookviTToria Biotherapeutics, Philadelphia, PA, USA.ORCID 0000-0001-9216-4560
Nicholas SicilianoviTToria Biotherapeutics, Philadelphia, PA, USA.ORCID 0009-0002-2971-0009
Antonia RotoloCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-2891-5793
Arati InamdarDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-7130-5392
Jaryse HarrisDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA, USA.ORCID 0009-0005-7235-3539
Ositadimma UgwuanyiCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.
Michael WangCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.
Alberto CarturanCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0003-2711-5724
Luca ParuzzoCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-6505-0194
Linhui ChenCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.
Hatcher J BallardDivision of Hematology and Oncology, Hospital of University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-7384-7363
Tatiana BlanchardCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.
Chong XuCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.
Mohamed Abdel-MohsenVaccine and Immunotherapy Center, Wistar Institute, Philadelphia, PA, USA.ORCID 0000-0002-9945-4314
Khatuna GabuniaCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0009-0008-1284-1268
Maria WysockaDepartment of Dermatology, Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0003-1376-2357
Gerald P LinetteCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0001-6147-6115
Beatriz CarrenoCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.
David M BarrettCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.
David T TeacheyDivision of Oncology, Children's Hospital of Philadelphia, PA, USA.ORCID 0000-0001-7373-8987
Avery D PoseyCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0001-8711-629X
Daniel J PowellCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-5966-8908
C Tor SauterCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-7638-3349
Stefano PileriDivision of Haematopathology, Istituto Europeo di Oncologia IRCCS, Italy.ORCID 0000-0001-8032-5128
Vinodh PillaiDivision of Hemato-pathology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
John SchollerCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-9725-6277
Alain H RookDepartment of Dermatology, Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-8356-0569
Stephen J SchusterCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-3376-8978
Stefan K BartaCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-3280-5271
Patrizia PorazziCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-1372-7482
Marco RuellaCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0003-4301-5811
Funding
UNIVERSITY OF PENNSYLVANIA CAN CTR SUPPORT GRANTP30CA016520 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Robert H. Vonderheide · 1985 to 2026
$222.3MVirus & Reservoirs CoreP30AI045008 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI DAVID S METZGER · 1999 to 2026
$78.6MProject 3: Combinatorial and gene-editing approaches to enhance the efficacy of CAR T cell therapy of multiple myeloma.P01CA214278 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Joseph Anthony Fraietta · 2017 to 2026
$26.8MHEMATOLOGY CLINICAL RESEARCH TRAINING PROGRAMT32HL007439 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI LAWRENCE F BRASS, PETER S KLEIN · 1985 to 2026
$17.1MMODULATION OF CD5 SIGNALING TO ENHANCE ADOPTIVE T-CELL THERAPIES FOR CANCERR37CA262362 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Marco Ruella · 2022 to 2026
$2.6MNCI NIH HHS P01 CA214278NCI NIH HHS P30 CA016520NCI NIH HHS R37 CA262362NHLBI NIH HHS T32 HL007439NIAID NIH HHS P30 AI045008
Abstract
Most patients treated with US Food and Drug Administration (FDA)-approved chimeric antigen receptor (CAR) T cells eventually experience disease progression. Furthermore, CAR T cells have not been curative against solid cancers and several hematological malignancies such as T cell lymphomas, which have very poor prognoses. One of the main barriers to the clinical success of adoptive T cell immunotherapies is CAR T cell dysfunction and lack of expansion and/or persistence after infusion. In this study, we found that CD5 inhibits CAR T cell activation and that knockout (KO) of CD5 using CRISPR-Cas9 enhances the antitumor effect of CAR T cells in multiple hematological and solid cancer models. Mechanistically, CD5 KO drives increased T cell effector function with enhanced cytotoxicity, in vivo expansion, and persistence, without apparent toxicity in preclinical models. These findings indicate that CD5 is a critical inhibitor of T cell function and a potential clinical target for enhancing T cell therapies.
Indexed as
CD5 AntigensImmunotherapy, AdoptiveT-LymphocytesAnimalsCell Line, TumorCRISPR-Cas SystemsFemaleHumansMiceReceptors, Chimeric AntigenCD5 AntigensCd5 protein, mouseReceptors, Chimeric Antigen
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