ArticleCancer cell2022
Expression of inducible factors reprograms CAR-T cells for enhanced function and safety.
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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 47 papers.
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47citing papers in PubMed
5.9field-weighted citation impact, top 3% of its field
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Who cites it
47 citing papers in PubMed, 62 citations in OpenAlex.
- T cell senescence and exhaustion: molecular mechanisms and immune rejuvenation for cancer immunotherapy.Signal transduction and targeted therapy · 2026Review
- Enhancing persistence while managing cytokine release syndrome to embrace next-generation CAR-T cell therapy.Journal of translational medicine · 2026Review
- In Vivo T-Cell Engineering: Revolution in Delivery Strategies and Clinical Translation.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Preventing trogocytosis by cathepsin B inhibition augments CAR T-cell function.Signal transduction and targeted therapy · 2026Article
- Integrating CAR-T therapy with PD-1/PD-L1 blockade: Mechanisms, synergy, and optimized strategies in NSCLC.iScience · 2026Review
- Methods and applications of patient-derived organoid models for immune microenvironment and immunotherapy research in multiple cancer types.Experimental hematology & oncology · 2026Review
- In vivo engineering of CAR-T cells: delivery strategies and clinical translation.Biomarker research · 2026Review
- Advancing adoptive T cell therapy in ovarian cancer: barriers, innovations, and emerging platforms.Journal for immunotherapy of cancer · 2026Review
- CAR T cell engineering approaches to minimise toxicities.Experimental biology and medicine (Maywood, N.J.) · 2026Review
- Chimeric antigen receptor cells as a tool for localized delivery of TNFα in solid cancer treatment.Human vaccines & immunotherapeutics · 2025Review
- Syngeneic CAR T cells engineered for persistent delivery of desired proteins.Journal of controlled release : official journal of the Controlled Release Society · 2025Article
- From Bench to Bedside: Emerging Paradigms in CAR-T Cell Therapy for Solid Malignancies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Preventing trogocytosis by cathepsin B inhibition augments CAR T cell function.bioRxiv : the preprint server for biology · 2025Article
- GPC2-Targeted CAR T Cells Engineered with NFAT-Inducible Membrane-Tethered IL15/IL21 Exhibit Enhanced Activity against Neuroblastoma.Cancer immunology research · 2025Article
- NRCAM variant defined by microexon skipping is a targetable cell surface proteoform in high-grade gliomas.Cell reports · 2025Article
- Improving CAR-T cell function through a targeted cytokine delivery system utilizing car target-modified extracellular vesicles.Experimental hematology & oncology · 2025Article
- Enhancing the potency of CAR-T cells against solid tumors through transcription factor engineering.JCI insight · 2025Review
- Mutant KRAS peptide targeted CAR-T cells engineered for cancer therapy.Cancer cell · 2025Article
- CAR T cell therapies in gastrointestinal cancers: current clinical trials and strategies to overcome challenges.Nature reviews. Gastroenterology & hepatology · 2025Review
- Insights into next-generation immunotherapy designs and tools: molecular mechanisms and therapeutic prospects.Journal of hematology & oncology · 2025Review
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Authors and funding
26 authors at 5 institutions in 2 countries.
Anže SmoleCenter for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Parker Institute for Cancer Immunotherapy, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. Electronic address: anze.smole@nib.si.
Alexander BentonCenter for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Mathilde A PoussinCenter for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Monika A EivaCenter for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Claudia MezzanotteInnovative Immunotherapies Unit, Division of Immunology, Transplantation, and Infectious Diseases, IRCCS Ospedale San Raffaele Scientific Institute, 20132 Milan, Italy.
Barbara CamisaInnovative Immunotherapies Unit, Division of Immunology, Transplantation, and Infectious Diseases, IRCCS Ospedale San Raffaele Scientific Institute, 20132 Milan, Italy.
Beatrice GrecoInnovative Immunotherapies Unit, Division of Immunology, Transplantation, and Infectious Diseases, IRCCS Ospedale San Raffaele Scientific Institute, 20132 Milan, Italy.
Prannda SharmaCenter for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Nicholas G MinutoloCenter for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Falon GrayCenter for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Adham S BearCenter for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Miren L BarojaCenter for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Parker Institute for Cancer Immunotherapy, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Casey CumminsCenter for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Parker Institute for Cancer Immunotherapy, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Chong XuCenter for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Parker Institute for Cancer Immunotherapy, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Francesca SanvitoPathology Unit, Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.
Andrea Lang GoldgewichtCenter for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Tatiana BlanchardCenter for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Alba Rodriguez-GarciaCenter for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Michael KlichinskyCenter for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Chiara BoniniExperimental Hematology Unit, Division of Immunology, Transplantation, and Infectious Diseases, IRCCS Ospedale San Raffaele Scientific Institute and University Vita-Salute San Raffaele, 20132 Milan, Italy.
Carl H JuneCenter for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Parker Institute for Cancer Immunotherapy, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Avery D PoseyCenter for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Parker Institute for Cancer Immunotherapy, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.
Gerald P LinetteCenter for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Parker Institute for Cancer Immunotherapy, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Beatriz M CarrenoCenter for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Parker Institute for Cancer Immunotherapy, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Monica CasucciInnovative Immunotherapies Unit, Division of Immunology, Transplantation, and Infectious Diseases, IRCCS Ospedale San Raffaele Scientific Institute, 20132 Milan, Italy.
Daniel J PowellCenter for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Parker Institute for Cancer Immunotherapy, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. Electronic address: poda@pennmedicine.upenn.edu.
Parker Institute for Cancer Immunotherapy · USUniversity of Pennsylvania · USIRCCS Ospedale San Raffaele · ITTranslational Therapeutics (United States) · USVita-Salute San Raffaele University · IT
Funding
IMMUNOBIOLOGY OF NORMAL AND NEOPLASTIC LYMPHOCYTEST32CA009140 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Malay Haldar, WARREN S PEAR · 1985 to 2026
$16.1MPREDOCTORAL TRAINING PROGRAM IN PHARMACOLOGYT32GM008076 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI BLENDY, JULIE A · 1985 to 2023
$10.8MIntegrated Discovery Pipeline for Tumor NeoantigensR01CA204261 · NCI · UNIVERSITY OF PENNSYLVANIA · PI CARRENO, BEATRIZ M., LINETTE, GERALD P · 2016 to 2020
$2.7MQuantitative control of CAR T cells via image-guided delivery and monitoringR01EB026892 · NIBIB · UNIVERSITY OF PENNSYLVANIA · PI FARWELL, MICHAEL DAVID, POWELL, DANIEL J. · 2018 to 2021
$2.6MPD-1 Blockade and Neoantigen-Specific T Cell ImmunityR21CA205794 · NCI · WASHINGTON UNIVERSITY · PI LINETTE, GERALD P · 2016 to 2018
$385kNCI NIH HHS R01 CA204261NCI NIH HHS R21 CA205794NCI NIH HHS T32 CA009140NIBIB NIH HHS R01 EB026892NIGMS NIH HHS T32 GM008076
Abstract
Despite the success of CAR-T cell cancer immunotherapy, challenges in efficacy and safety remain. Investigators have begun to enhance CAR-T cells with the expression of accessory molecules to address these challenges. Current systems rely on constitutive transgene expression or multiple viral vectors, resulting in unregulated response and product heterogeneity. Here, we develop a genetic platform that combines autonomous antigen-induced production of an accessory molecule with constitutive CAR expression in a single lentiviral vector called Uni-Vect. The broad therapeutic application of Uni-Vect is demonstrated in vivo by activation-dependent expression of (1) an immunostimulatory cytokine that improves efficacy, (2) an antibody that ameliorates cytokine-release syndrome, and (3) transcription factors that modulate T cell biology. Uni-Vect is also implemented as a platform to characterize immune receptors. Overall, we demonstrate that Uni-Vect provides a foundation for a more clinically actionable next-generation cellular immunotherapy.
Indexed as
Immunotherapy, AdoptiveReceptors, Antigen, T-CellCytokinesGenetic VectorsHumansT-LymphocytesCytokinesReceptors, Antigen, T-CellarmoredCAR-T CellsCRSIL-12IL-6inducibleNFATsingle lentiviral expression systemTCRtranscription factor
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