Evidence map›Paper›PMID 33328215›Full record

ArticleCancer discovery2021

CRISPR Screening of CAR T Cells and Cancer Stem Cells Reveals Critical Dependencies for Cell-Based Therapies.

Dongrui Wang, Briana C Prager, Ryan C Gimple, Brenda Aguilar, Darya Alizadeh, Hongzhen Tang, Deguan Lv, Renate Starr, Alfonso Brito, Qiulian Wu and 9 more

Open access · greenAbstract read
In one paragraph

Article in Cancer discovery, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
129citing papers in PubMed, 2 pooled it
6.2field-weighted citation impact, top 3% of its field
1 · What the graph read from 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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

129 citing papers in PubMed, 2 syntheses or guidelines pooled it, 166 citations in OpenAlex.

  1. Mapping the clinical landscape of multifunctional CAR T cells: Targets, trends, and synergies.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Pooled it
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  3. Overcoming T cell exhaustion and senescence in CAR T cell therapy for solid tumors.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
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69 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors at 4 institutions in 2 countries.

Dongrui Wang *T Cell Therapeutics Research Labs, Cellular Immunotherapy Center, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, California.
Briana C Prager *Division of Regenerative Medicine, Department of Medicine, University of California, San Diego, San Diego, California.
Ryan C GimpleDivision of Regenerative Medicine, Department of Medicine, University of California, San Diego, San Diego, California.ORCID 0000-0002-7189-3243
Brenda AguilarT Cell Therapeutics Research Labs, Cellular Immunotherapy Center, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, California.
Darya AlizadehT Cell Therapeutics Research Labs, Cellular Immunotherapy Center, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, California.
Hongzhen TangKey Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China.
Deguan LvDivision of Regenerative Medicine, Department of Medicine, University of California, San Diego, San Diego, California.
Renate StarrT Cell Therapeutics Research Labs, Cellular Immunotherapy Center, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, California.ORCID 0000-0002-2200-6900
Alfonso BritoT Cell Therapeutics Research Labs, Cellular Immunotherapy Center, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, California.
Qiulian WuDivision of Regenerative Medicine, Department of Medicine, University of California, San Diego, San Diego, California.
Leo J Y KimDivision of Regenerative Medicine, Department of Medicine, University of California, San Diego, San Diego, California.
Zhixin QiuDivision of Regenerative Medicine, Department of Medicine, University of California, San Diego, San Diego, California.ORCID 0000-0001-7103-8004
Peng LinKey Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China.
Michael H LorenziniDivision of Regenerative Medicine, Department of Medicine, University of California, San Diego, San Diego, California.ORCID 0000-0002-7666-6584
Behnam BadieDivision of Neurosurgery, Department of Surgery, City of Hope, Duarte, California.
Stephen J FormanT Cell Therapeutics Research Labs, Cellular Immunotherapy Center, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, California.
Qi XieKey Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China. drjeremyrich@gmail.com xieqi@westlake.edu.cn cbrown@coh.org.
Christine E Brown *T Cell Therapeutics Research Labs, Cellular Immunotherapy Center, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, California. drjeremyrich@gmail.com xieqi@westlake.edu.cn cbrown@coh.org.ORCID 0000-0003-4915-8207
Jeremy N Rich *Division of Regenerative Medicine, Department of Medicine, University of California, San Diego, San Diego, California. drjeremyrich@gmail.com xieqi@westlake.edu.cn cbrown@coh.org.
University of California San Diego · USCity of Hope · USWestlake University · CNCity Of Hope National Medical Center · US

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007250 · NIGMS · CASE WESTERN RESERVE UNIVERSITY · PI HUANG, ALEX YEE-CHEN · 1985 to 2023
$33.4M
Dynamic Complexity of Brain Tumor Stem Cells (R35CA197718)R35CA197718 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI RICH, JEREMY N · 2015 to 2021
$6.4M
Clinical evaluation of IL13Ra2-targeted CAR T cell therapy in combination with nivolumab in patients with recurrent malignant gliomaR01CA236500 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI BADIE, BEHNAM, BROWN, CHRISTINE · 2019 to 2024
$3.3M
Targeting the Circadian Rhythm in Glioblastoma Stem Cells (R01CA238662)R01CA238662 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KAY, STEVE A, RICH, JEREMY N · 2020 to 2024
$2.8M
Dual Targeting of Brain Tumor Initiating Cells through Inhibition of BMI1 and EZH2 (R01NS103434)R01NS103434 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI RICH, JEREMY N · 2017 to 2021
$1.7M
The Unfolded Protein Response in GlioblastomaF30CA217066 · NCI · CLEVELAND CLINIC LERNER COM-CWRU · PI PRAGER, BRIANA · 2017 to 2020
$195k
Epigenetic Regulation of Lipid Metabolism in Glioma Stem CellsF30CA217065 · NCI · CLEVELAND CLINIC LERNER COM-CWRU · PI GIMPLE, RYAN CHRISTOPHER · 2017 to 2020
$189k
Targeting TCA cycle in Brain Tumor Initiating CellsF30CA203101 · NCI · CLEVELAND CLINIC LERNER COM-CWRU · PI KIM, JIN YOUNG LEO · 2016 to 2019
$160k
The role of T helper cells in mediating effective immune checkpoint blockade therapy against cancerK00CA234923 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI WANG, DONGRUI · 2021 to 2021
$88k
Refinement of CAR-T-Cell therapy targeting glioblastomasF99CA234923 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI WANG, DONGRUI · 2018 to 2019
$59k
NCI NIH HHS F30 CA203101NCI NIH HHS F30 CA217065NCI NIH HHS F30 CA217066NCI NIH HHS F99 CA234923NCI NIH HHS K00 CA234923NCI NIH HHS R01 CA236500NCI NIH HHS R01 CA238662NCI NIH HHS R35 CA197718NIGMS NIH HHS T32 GM007250NINDS NIH HHS R01 NS103434
6 · The paper itself

Abstract

Glioblastoma (GBM) contains self-renewing GBM stem cells (GSC) potentially amenable to immunologic targeting, but chimeric antigen receptor (CAR) T-cell therapy has demonstrated limited clinical responses in GBM. Here, we interrogated molecular determinants of CAR-mediated GBM killing through whole-genome CRISPR screens in both CAR T cells and patient-derived GSCs. Screening of CAR T cells identified dependencies for effector functions, including TLE4 and IKZF2. Targeted knockout of these genes enhanced CAR antitumor efficacy. Bulk and single-cell RNA sequencing of edited CAR T cells revealed transcriptional profiles of superior effector function and inhibited exhaustion responses. Reciprocal screening of GSCs identified genes essential for susceptibility to CAR-mediated killing, including RELA and NPLOC4, the knockout of which altered tumor-immune signaling and increased responsiveness of CAR therapy. Overall, CRISPR screening of CAR T cells and GSCs discovered avenues for enhancing CAR therapeutic efficacy against GBM, with the potential to be extended to other solid tumors. SIGNIFICANCE: Reciprocal CRISPR screening identified genes in both CAR T cells and tumor cells regulating the potency of CAR T-cell cytotoxicity, informing molecular targeting strategies to potentiate CAR T-cell antitumor efficacy and elucidate genetic modifications of tumor cells in combination with CAR T cells to advance immuno-oncotherapy.

Indexed as

Clustered Regularly Interspaced Short Palindromic RepeatsBrain NeoplasmsCell- and Tissue-Based TherapyCell Line, TumorGlioblastomaHumansNeoplastic Stem CellsReceptors, Chimeric AntigenReceptors, Chimeric Antigen

Identifiers

PMID33328215
PMCPMC8406797
OpenAlexW3112226569

What OpenQuestion holds

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Registered trials

None linked

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.