Evidence map›Paper›PMID 35483375›Full record

ArticleCell2022

Enhanced safety and efficacy of protease-regulated CAR-T cell receptors.

Louai Labanieh, Robbie G Majzner, Dorota Klysz, Elena Sotillo, Chris J Fisher, José G Vilches-Moure, Kaithlen Zen B Pacheco, Meena Malipatlolla, Peng Xu, Jessica H Hui and 12 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 146 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
146citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

146 citing papers in PubMed, 1 synthesis or guideline pooled it.

  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
  2. Trial
  3. Review
  4. Article
  5. Review
  6. Article
  7. A Drug-Gated, Modular STAb-T Immunotherapy With External Control.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  8. Review
  9. Article
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  11. Review
  12. Review
  13. Article
  14. Review
  15. Article
  16. Cell Cycle Sensing Shapes Human T Cell Fate and Exhaustion Programs.bioRxiv : the preprint server for biology · 2026
    Article
  17. Article
  18. Review
  19. Review
  20. Humanized extracellular vesicles for efficient RNA delivery.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article

86 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors.

Louai LabaniehDepartment of Bioengineering, Stanford University, Stanford, CA 94305, USA; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Robbie G MajznerCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Dorota KlyszCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Elena SotilloCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Chris J FisherCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
José G Vilches-MoureDepartment of Comparative Medicine, School of Medicine, Stanford University, Stanford, CA 94305, USA.
Kaithlen Zen B PachecoCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Meena MalipatlollaCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Peng XuCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Jessica H HuiCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Tara MurtyCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Medical Scientist Training Program, Stanford University School of Medicine, Stanford, CA 94305, USA; Biophysics Program, Stanford University School of Medicine, Stanford, CA 94305, USA.
Johanna TheruvathCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Nishant MehtaDepartment of Bioengineering, Stanford University, Stanford, CA 94305, USA.
Sean A Yamada-HunterCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Evan W WeberCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Sabine HeitzenederCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Kevin R ParkerCenter for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, CA 94305, USA.
Ansuman T SatpathyDepartment of Pathology, Stanford University, Stanford, CA 94305, USA.
Howard Y ChangCenter for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
Michael Z LinDepartment of Bioengineering, Stanford University, Stanford, CA 94305, USA; Department of Neurobiology, Stanford University, Stanford, CA 94305, USA; Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Jennifer R CochranDepartment of Bioengineering, Stanford University, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA.
Crystal L MackallCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: cmackall@stanford.edu.

Funding

Understanding and Overcoming Resistance to Immunotherapies in Childhood CancersU54CA232568 · NCI · CHILDREN'S HOSP OF PHILADELPHIA · PI MACKALL, CRYSTAL, MARIS, JOHN M · 2018 to 2022
$13.1M
4DN Interrogation of T Cell Exhaustion in CancerU01CA260852 · NCI · STANFORD UNIVERSITY · PI SATPATHY, ANSUMAN · 2020 to 2024
$2.6M
Hijacking the T cell machinery for logic-gated CAR T cell controlDP2CA272092 · NCI · STANFORD UNIVERSITY · PI MAJZNER, ROBBIE G. · 2021 to 2024
$2.5M
NCI NIH HHS DP2 CA272092NCI NIH HHS U01 CA260852NCI NIH HHS U54 CA232568
6 · The paper itself

Abstract

Regulatable CAR platforms could circumvent toxicities associated with CAR-T therapy, but existing systems have shortcomings including leakiness and attenuated activity. Here, we present SNIP CARs, a protease-based platform for regulating CAR activity using an FDA-approved small molecule. Design iterations yielded CAR-T cells that manifest full functional capacity with drug and no leaky activity in the absence of drug. In numerous models, SNIP CAR-T cells were more potent than constitutive CAR-T cells and showed diminished T cell exhaustion and greater stemness. In a ROR1-based CAR lethality model, drug cessation following toxicity onset reversed toxicity, thereby credentialing the platform as a safety switch. In the same model, reduced drug dosing opened a therapeutic window that resulted in tumor eradication in the absence of toxicity. SNIP CARs enable remote tuning of CAR activity, which provides solutions to safety and efficacy barriers that are currently limiting progress in using CAR-T cells to treat solid tumors.

Indexed as

NeoplasmsReceptors, Chimeric AntigenHumansImmunotherapy, AdoptivePeptide HydrolasesReceptors, Antigen, T-CellT-LymphocytesPeptide HydrolasesReceptors, Antigen, T-CellReceptors, Chimeric Antigenbrain tumorsCAR-T therapycellular immunotherapychimeric antigen receptorsimmune cell engineeringsolid cancerssynthetic biologyT cell differentiationT cell exhaustion

Identifiers

PMID35483375
PMCPMC9467936

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.