Evidence map›Paper›PMID 28389661›Full record

ArticleScientific reports2017

CRISPR/Cas9-mediated PD-1 disruption enhances anti-tumor efficacy of human chimeric antigen receptor T cells.

Levi J Rupp, Kathrin Schumann, Kole T Roybal, Rachel E Gate, Chun J Ye, Wendell A Lim, Alexander Marson

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 452 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
452citing papers in PubMed, 1 pooled it
33.6field-weighted citation impact, top 1% 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

452 citing papers in PubMed, 1 synthesis or guideline pooled it, 722 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
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392 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

7 authors at 4 institutions in 1 country.

Levi J RuppDepartment of Cellular & Molecular Pharmacology, San Francisco, CA, USA.
Kathrin SchumannDiabetes Center, University of California San Francisco, San Francisco, CA, 94143, USA.
Kole T RoybalDepartment of Cellular & Molecular Pharmacology, San Francisco, CA, USA.
Rachel E GateDepartment of Epidemiology and Biostatistics, Department of Bioengineering and Therapeutic Sciences, Institute for Human Genetics, University of California, San Francisco, CA, 94143, USA.
Chun J YeDepartment of Epidemiology and Biostatistics, Department of Bioengineering and Therapeutic Sciences, Institute for Human Genetics, University of California, San Francisco, CA, 94143, USA.
Wendell A LimDepartment of Cellular & Molecular Pharmacology, San Francisco, CA, USA. Wendell.lim@ucsf.edu.
Alexander MarsonHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, 94158, USA.
University of California, San Francisco · USHoward Hughes Medical Institute · USInnovative Genomics Institute · USUCSF Helen Diller Family Comprehensive Cancer Center · US

Funding

Cellular Control:Synthetic Signaling/Motility (RMI)PN2EY016546 · NEI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LIM, WENDELL A · 2005 to 2014
$16.0M
BMI Bioinformatics Training GrantsT32GM067547 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HERNANDEZ, RYAN D. · 2003 to 2022
$6.6M
PROTEIN RECOGNITION IN SIGNAL TRANSDUCTIONR01GM055040 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LIM, WENDELL A · 1997 to 2015
$3.5M
Redesigning the T cell: Using Synthetic Biology to Engineer Therapeutic CellsR01CA196277 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LIM, WENDELL A · 2014 to 2018
$3.3M
CRISPR-based genome and transcriptional engineering of human T cells to enhance cancer immunotherapy approachesF32AI120352 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI RUPP, LEVI JORDAN · 2016 to 2016
$13k
Howard Hughes Medical InstituteNCI NIH HHS R01 CA196277NEI NIH HHS PN2 EY016546NIAID NIH HHS F32 AI120352NIGMS NIH HHS R01 GM055040NIGMS NIH HHS T32 GM067547
6 · The paper itself

Abstract

Immunotherapies with chimeric antigen receptor (CAR) T cells and checkpoint inhibitors (including antibodies that antagonize programmed cell death protein 1 [PD-1]) have both opened new avenues for cancer treatment, but the clinical potential of combined disruption of inhibitory checkpoints and CAR T cell therapy remains incompletely explored. Here we show that programmed death ligand 1 (PD-L1) expression on tumor cells can render human CAR T cells (anti-CD19 4-1BBζ) hypo-functional, resulting in impaired tumor clearance in a sub-cutaneous xenograft model. To overcome this suppressed anti-tumor response, we developed a protocol for combined Cas9 ribonucleoprotein (Cas9 RNP)-mediated gene editing and lentiviral transduction to generate PD-1 deficient anti-CD19 CAR T cells. Pdcd1 (PD-1) disruption augmented CAR T cell mediated killing of tumor cells in vitro and enhanced clearance of PD-L1+ tumor xenografts in vivo. This study demonstrates improved therapeutic efficacy of Cas9-edited CAR T cells and highlights the potential of precision genome engineering to enhance next-generation cell therapies.

Indexed as

CRISPR-Cas SystemsGene TargetingAnimalsAntigens, CD19Antigens, NeoplasmB7-H1 AntigenBiomarkersCell Line, TumorFemaleGene ExpressionGene Knockdown TechniquesHumansImmunophenotypingMiceMice, KnockoutNeoplasmsAntigens, CD19Antigens, NeoplasmB7-H1 AntigenBiomarkersCD274 protein, humanPDCD1 protein, humanProgrammed Cell Death 1 ReceptorReceptors, Antigen, T-Cell

Identifiers

PMID28389661
PMCPMC5428439
OpenAlexW2604982880

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.