ArticleBlood advances2023
Activation priming and cytokine polyfunctionality modulate the enhanced functionality of low-affinity CD19 CAR T cells.
Article in Blood advances, 2023. 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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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
17 citing papers in PubMed.
- Human lung γδ T cells maintain functionality during inflammatory lung disease.bioRxiv : the preprint server for biology · 2026Article
- PiP-Plex: A Particle-in-Particle System for Multiplexed Quantification of Proteins Secreted by Single Cells.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- Bispecific antibodies and CAR T cells targeting a TP53 mutation-associated neoantigen show discordant affinity requirements.The Journal of clinical investigation · 2026Article
- Predictive markers for the efficacy of CAR T-cell therapy: the interplay between CAR T-cell fitness and systemic immunity.Blood advances · 2025Review
- Enhanced solid tumor cell targeting by a neoepitope-encoding oncolytic measles virus combined with CAR therapy.Molecular therapy. Oncology · 2025Article
- Development of antigen multimers for detection and evaluation of CAR T cells.Cancer immunology, immunotherapy : CII · 2025Article
- Facts and Hopes: CAR T-Cell Therapy and Immune Contexture in Non-Hodgkin Lymphoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Review
- Antitumor Activities of a Humanized Cancer-Specific Anti-HER2 Monoclonal Antibody, humHInternational journal of molecular sciences · 2025Article
- New insights on potency assays from recent advances and discoveries in CAR T-cell therapy.Frontiers in immunology · 2025Review
- Analysis of polyfunctionality for enhanced BAFF-R CAR T-cell therapy for hematologic malignancies.Blood advances · 2024Article
- CAR-T cell manufacturing landscape-Lessons from the past decade and considerations for early clinical development.Molecular therapy. Methods & clinical development · 2024Review
- CAR T cells and T cells phenotype and function are impacted by glucocorticoid exposure with different magnitude.Journal of translational medicine · 2024Article
- Novel and multiple targets for chimeric antigen receptor-based therapies in lymphoma.Frontiers in oncology · 2024Review
- Biomarkers for prediction of CAR T therapy outcomes: current and future perspectives.Frontiers in immunology · 2024Review
- Article
- Preventing relapse after CD19 CAR T-cell therapy for pediatric ALL: the role of transplant and enhanced CAR T cells.Hematology. American Society of Hematology. Education Program · 2023Review
- Transcriptomic Approaches in Studies on and Applications of Chimeric Antigen Receptor T Cells.Biomedicines · 2023Review
Corrections and comments
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Authors and funding
18 authors.
Funding
Abstract
We recently described a low-affinity second-generation CD19 chimeric antigen receptor (CAR) CAT that showed enhanced expansion, cytotoxicity, and antitumor efficacy compared with the high-affinity (FMC63-based) CAR used in tisagenlecleucel, in preclinical models. Furthermore, CAT demonstrated an excellent toxicity profile, enhanced in vivo expansion, and long-term persistence in a phase 1 clinical study. To understand the molecular mechanisms behind these properties of CAT CAR T cells, we performed a systematic in vitro characterization of the transcriptomic (RNA sequencing) and protein (cytometry by time of flight) changes occurring in T cells expressing low-affinity vs high-affinity CD19 CARs following stimulation with CD19-expressing cells. Our results show that CAT CAR T cells exhibit enhanced activation to CD19 stimulation and a distinct transcriptomic and protein profile, with increased activation and cytokine polyfunctionality compared with FMC63 CAR T cells. We demonstrate that the enhanced functionality of low-affinity CAT CAR T cells is a consequence of an antigen-dependent priming induced by residual CD19-expressing B cells present in the manufacture.
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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.