Evidence map›Paper›PMID 36350984›Full record

ArticleScience translational medicine2022

Pooled screening of CAR T cells identifies diverse immune signaling domains for next-generation immunotherapies.

Daniel B Goodman, Camillia S Azimi, Kendall Kearns, Alexis Talbot, Kiavash Garakani, Julie Garcia, Nisarg Patel, Byungjin Hwang, David Lee, Emily Park and 7 more

Open access · greenAbstract read
In one paragraph

Article in Science translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed
7.7field-weighted citation impact, top 2% 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

57 citing papers in PubMed, 84 citations in OpenAlex.

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  18. Imaging the fate of CAR-T cellsFrontiers in immunology · 2026
    Review
  19. A unified genetic perturbation language for human cellular programming.bioRxiv : the preprint server for biology · 2025
    Article
  20. Article
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

17 authors at 2 institutions in 3 countries.

Daniel B GoodmanDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA.ORCID 0000-0003-3759-6883
Camillia S AzimiDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA.ORCID 0000-0003-0406-5840
Kendall KearnsDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA.ORCID 0000-0002-4633-4554
Alexis TalbotDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA.ORCID 0000-0001-6734-413X
Kiavash GarakaniDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA.ORCID 0000-0002-2896-3234
Julie GarciaDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA.ORCID 0000-0002-1103-3970
Nisarg PatelSchool of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.ORCID 0000-0003-1697-6481
Byungjin HwangInstitute for Human Genetics (IHG), University of California, San Francisco, San Francisco, CA 94143, USA.
David LeeInstitute for Human Genetics (IHG), University of California, San Francisco, San Francisco, CA 94143, USA.ORCID 0000-0001-6539-4272
Emily ParkDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA.ORCID 0000-0001-8683-0598
Vivasvan S VykuntaParker Institute for Cancer Immunotherapy, San Francisco, CA 94143, USA.ORCID 0000-0002-5409-8635
Brian R ShyParker Institute for Cancer Immunotherapy, San Francisco, CA 94143, USA.ORCID 0000-0001-9569-3708
Chun Jimmie YeParker Institute for Cancer Immunotherapy, San Francisco, CA 94143, USA.ORCID 0000-0001-6560-3783
Justin EyquemDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA.ORCID 0000-0001-8262-1190
Alexander MarsonDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA.ORCID 0000-0002-2734-5776
Jeffrey A BluestoneDiabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA.ORCID 0000-0001-8793-7848
Kole T RoybalDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA.ORCID 0000-0003-3030-7954
University of California, San Francisco · USGladstone Institutes · US

Funding

Research BaseP30DK063720 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VAISSE, CHRISTIAN · 2003 to 2019
$21.8M
MOLECULAR AND CELLULAR IMMUNOLOGYT32AI007334 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CYSTER, JASON G · 1988 to 2023
$11.0M
RESOURCE-BASED CENTER FOR THE ADVANCEMENT OF PRECISION MEDICINE IN RHEUMATOLOGYP30AR070155 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Mary C Nakamura · 2016 to 2026
$8.2M
User-control and safetyU54CA244438 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LIM, WENDELL A · 2019 to 2022
$7.8M
Mapping gene-by-environment interactions using multiplexed single cell RNA-sequencingR01HG011239 · NHGRI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI YE, CHUN JIMMIE · 2020 to 2023
$4.1M
Genetic regulation and immunological function of ERAP2 haplotypesR01AI136972 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI YE, CHUN JIMMIE · 2018 to 2022
$3.5M
Engineering the Next-generation of Custom Immune Cell TherapiesDP2CA239143 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ROYBAL, KOLE T · 2018 to 2018
$2.4M
Fine mapping rheumatic disease variants using functional genomic sequencingR01AR071522 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI YE, CHUN JIMMIE · 2017 to 2020
$1.5M
Cancer Research UK 27145NCI NIH HHS DP2 CA239143NCI NIH HHS U54 CA244438NHGRI NIH HHS R01 HG011239NIAID NIH HHS R01 AI136972NIAID NIH HHS T32 AI007334NIAMS NIH HHS P30 AR070155NIAMS NIH HHS R01 AR071522NIDDK NIH HHS P30 DK063720
6 · The paper itself

Abstract

Chimeric antigen receptors (CARs) repurpose natural signaling components to retarget T cells to refractory cancers but have shown limited efficacy in persistent, recurrent malignancies. Here, we introduce "CAR Pooling," a multiplexed approach to rapidly identify CAR designs with clinical potential. Forty CARs with signaling domains derived from a range of immune cell lineages were evaluated in pooled assays for their ability to stimulate critical T cell effector functions during repetitive stimulation that mimics long-term tumor antigen exposure. Several domains were identified from the tumor necrosis factor (TNF) receptor family that have been primarily associated with B cells. CD40 enhanced proliferation, whereas B cell-activating factor receptor (BAFF-R) and transmembrane activator and CAML interactor (TACI) promoted cytotoxicity. These functions were enhanced relative to clinical benchmarks after prolonged antigen stimulation, and CAR T cell signaling through these domains fell into distinct states of memory, cytotoxicity, and metabolism. BAFF-R CAR T cells were enriched for a highly cytotoxic transcriptional signature previously associated with positive clinical outcomes. We also observed that replacing the 4-1BB intracellular signaling domain with the BAFF-R signaling domain in a clinically validated B cell maturation antigen (BCMA)-specific CAR resulted in enhanced activity in a xenotransplant model of multiple myeloma. Together, these results show that CAR Pooling is a general approach for rapid exploration of CAR architecture and activity to improve the efficacy of CAR T cell therapies.

Indexed as

Neoplasm Recurrence, LocalReceptors, Chimeric AntigenB-Cell Maturation AntigenHumansImmunotherapyImmunotherapy, AdoptiveSignal TransductionT-LymphocytesB-Cell Maturation AntigenReceptors, Chimeric Antigen

Identifiers

PMID36350984
PMCPMC9939256
OpenAlexW4308623157

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.