Trial reportMolecular therapy : the journal of the American Society of Gene Therapy2022
PD-1 and TIGIT downregulation distinctly affect the effector and early memory phenotypes of CD19-targeting CAR T cells.
Trial report in Molecular therapy : the journal of the American Society of Gene Therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04836507 (An Open-label, Multi-center, Single-arm Phase 1/2 Study to Assess Tolerability, Safety and Efficacy of CRC01 in Adult Patients With Relapsed or Refractory Large B-cell Lymphoma and B-cell Acute Lymphoblastic Leukemia), which is not on this map. Cited by 65 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
An Open-label, Multi-center, Single-arm Phase 1/2 Study to Assess Tolerability, Safety and Efficacy of CRC01 in Adult Patients With Relapsed or Refractory Large B-cell Lymphoma and B-cell Acute Lymphoblastic Leukemia
Who cites it
65 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.
- Strategies and mechanisms for the enhancement of chimeric antigen receptor T-cell functions.Science China. Life sciences · 2026Pooled it
- Augmenting CAR T cell functionality and metabolism through CD39 downtuning.Molecular therapy. Oncology · 2026Article
- Anbalcabtagene Autoleucel: First Approval.Molecular diagnosis & therapy · 2026Article
- The Right Key, the Wrong Lock: TIGIT Checkpoint Blockade and the Road to Precision Immunotherapy.Pharmaceutics · 2026Review
- Mechanisms, optimization strategies, and salvage options for CAR-T cell therapy.Biomarker research · 2026Review
- In vivo CAR-T therapy: from molecular design to precision delivery.Journal of nanobiotechnology · 2026Review
- Antigen-binding affinity is a key determinant of the durable antitumor activity of CD5 CAR-T cells.Molecular therapy. Oncology · 2026Article
- Microbiome and metabolite biomarkers of CAR T-cell therapy outcomes in relapsed/refractory diffuse large B-cell lymphoma.Blood advances · 2026Article
- Microenvironmental regulation of solid tumour resistance to CAR T cell therapy.Nature reviews. Immunology · 2026Review
- Nanoparticles-enhanced CAR-T cell therapy: current advances and future directions.Biomarker research · 2026Review
- Role of tumor microenvironment in regulator of tumor progression and immunotherapy.Discover oncology · 2026Review
- Targeting the Dynamics Between TAMs and CAR-T Cells in Solid Tumor Therapies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Immunosuppressive cells as barriers to cancer therapy: mechanisms and emerging solutions.Frontiers in immunology · 2026Review
- The impact of the large B-cell lymphoma tumor microenvironment on efficacy of CD19-directed CAR-T immunotherapy.Frontiers in immunology · 2026Review
- Research progress on resistance mechanisms to CAR-T cell therapy in diffuse large B-cell lymphoma.Frontiers in oncology · 2026Review
- Engineering CAR-T cells for solid tumors: overcoming antigenic, trafficking, and microenvironmental barriers.Frontiers in immunology · 2026Review
- Next-generation CAR-T cells design: leveraging tumor features for enhanced efficacy.Molecular cancer · 2025Review
- Improving CAR T cell therapy against malignancies through gene knock-down/out strategies: a systematic review.Cancer cell international · 2025Review
- Cryopreservation of siRNA-Treated Cells Is Feasible.Nucleic acid therapeutics · 2025Article
- TIGIT blockade in the context of BCMA-CART cell therapy does not augment efficacy in a multiple myeloma mouse model.Oncoimmunology · 2025Article
5 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
14 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CD19-targeting chimeric antigen receptor (CAR) T cells have become an important therapeutic option for patients with relapsed and refractory B cell malignancies. However, a significant portion of patients still do not benefit from the therapy owing to various resistance mechanisms, including high expression of multiple inhibitory immune checkpoint receptors. Here, we report a lentiviral two-in-one CAR T approach in which two checkpoint receptors are downregulated simultaneously by a dual short hairpin RNA cassette integrated into a CAR vector. Using this system, we evaluated CD19-targeting CAR T cells in the context of four different checkpoint combinations-PD-1/TIM-3, PD-1/LAG-3, PD-1/CTLA-4, and PD-1/TIGIT-and found that CAR T cells with PD-1/TIGIT downregulation uniquely exerted synergistic antitumor effects. Importantly, functional and phenotypic analyses suggested that downregulation of PD-1 enhances short-term effector function, whereas downregulation of TIGIT is primarily responsible for maintaining a less differentiated/exhausted state, providing a potential mechanism for the observed synergy. The PD-1/TIGIT-downregulated CAR T cells generated from diffuse large B cell lymphoma patient-derived T cells also showed robust antitumor activity and significantly improved persistence in vivo. The efficacy and safety of PD-1/TIGIT-downregulated CD19-targeting CAR T cells are currently being evaluated in adult patients with relapsed or refractory large B cell lymphoma (ClinicalTrials.gov: NCT04836507).
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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.