ArticleBlood2020
Integrated drug profiling and CRISPR screening identify essential pathways for CAR T-cell cytotoxicity.
Article in Blood, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 148 papers.
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Who cites it
148 citing papers in PubMed, 215 citations in OpenAlex.
- Final results of a phase 2 clinical trial of LCL161, an oral SMAC mimetic for patients with myelofibrosis.Blood advances · 2021Trial
- XIAP inhibition augments personalized neoantigen vaccine-driven antitumor immunity in orthotopic hepatocellular carcinoma.Journal for immunotherapy of cancer · 2026Article
- High-Content CRISPR Screening: Methods and Applications.MedComm · 2026Review
- Tisa-cel and axi-cel CAR structure influences the development of resistance to CD19-CAR-T therapy.Leukemia · 2026Article
- Iron-mediated ferroptosis impairs CAR-T cell function and antitumor efficacy.Nature cancer · 2026Article
- Necroptotic cell death and immunomodulator release induced by T-cell engaging anti-lymphoma therapies.Cell death & disease · 2026Article
- Enhancing persistence while managing cytokine release syndrome to embrace next-generation CAR-T cell therapy.Journal of translational medicine · 2026Review
- Challenges and advances in CAR-T cell therapy for B-ALL.Biomarker research · 2026Review
- A convergent uPAR-positive tumor ecosystem creates broad vulnerability to CAR T cell therapy.Cell · 2026Article
- Mutant calreticulin enables potent and selective CAR-T cell therapy in preclinical models of myeloproliferative neoplasms.Journal for immunotherapy of cancer · 2026Article
- High-throughput screening to engineer optimal T cell therapies: current knowledge and future prospects.Frontiers in oncology · 2026Review
- Clathrin mediated endocytosis targeting chimera for targeted membrane proteins degradation and enhance CAR-T cell anti-tumor therapy.Theranostics · 2026Article
- Advances in Biomarkers for CAR-T Treatment Resistance in Diffuse Large B-Cell Lymphoma.Mini reviews in medicinal chemistry · 2026Review
- Evaluation of dasatinib and ponatinib for the control of CD123 CAR-T cell functionalities.Molecular therapy. Oncology · 2025Article
- Pyroptosis in cancer therapy: a double-edged sword for immune activation and tumor progression.Molecular cancer · 2025Review
- DLBCL Cells Emerge after CD19 CAR T Cells with Cross-Antigen Resistance and a Gene Signature Predictive of Clinical CAR T-cell Response.Blood cancer discovery · 2025Article
- Slc7a5 promotes T cell anti-tumor immunity through sustaining cytotoxic T lymphocyte effector function.Oncogene · 2025Article
- CAR-engineered lymphocyte persistence is governed by a FAS ligand-FAS autoregulatory circuit.Nature cancer · 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
- Mechanisms of Resistance to CAR T-Cells and How to Overcome Them.Methods and protocols · 2025Review
88 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chimeric antigen receptor (CAR) T-cell therapy has proven effective in relapsed and refractory B-cell malignancies, but resistance and relapses still occur. Better understanding of mechanisms influencing CAR T-cell cytotoxicity and the potential for modulation using small-molecule drugs could improve current immunotherapies. Here, we systematically investigated druggable mechanisms of CAR T-cell cytotoxicity using >500 small-molecule drugs and genome-scale CRISPR-Cas9 loss-of-function screens. We identified several tyrosine kinase inhibitors that inhibit CAR T-cell cytotoxicity by impairing T-cell signaling transcriptional activity. In contrast, the apoptotic modulator drugs SMAC mimetics sensitized B-cell acute lymphoblastic leukemia and diffuse large B-cell lymphoma cells to anti-CD19 CAR T cells. CRISPR screens identified death receptor signaling through FADD and TNFRSF10B (TRAIL-R2) as a key mediator of CAR T-cell cytotoxicity and elucidated the RIPK1-dependent mechanism of sensitization by SMAC mimetics. Death receptor expression varied across genetic subtypes of B-cell malignancies, suggesting a link between mechanisms of CAR T-cell cytotoxicity and cancer genetics. These results implicate death receptor signaling as an important mediator of cancer cell sensitivity to CAR T-cell cytotoxicity, with potential for pharmacological targeting to enhance cancer immunotherapy. The screening data provide a resource of immunomodulatory properties of cancer drugs and genetic mechanisms influencing CAR T-cell cytotoxicity.
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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.