Evidence map›Paper›PMID 42143019›Full record

ArticleCell2026

Cell-autonomous control of CAR signaling and receptor shedding via ADAM17-mediated proteolysis.

Jeremy R Bjelajac, Adrià Cañellas-Socias, Preeti Nehra, Kevin Reynolds, Meena Malipatlolla, Naiara Martinez Velez, Diane C Manjarrez, Katie Ho, Peng Xu, Jennifer L Hamad and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–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

1 citing paper in PubMed.

  1. 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

14 authors.

Jeremy R BjelajacStem Cell and Regenerative Medicine Graduate Program, Stanford University School of Medicine, Stanford, CA, USA; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA; Weill West Coast Cancer Hub, Stanford, CA, USA.
Adrià Cañellas-SociasCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA; Weill West Coast Cancer Hub, Stanford, CA, USA.
Preeti NehraCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
Kevin ReynoldsCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
Meena MalipatlollaCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
Naiara Martinez VelezCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
Diane C ManjarrezCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
Katie HoDepartment of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
Peng XuCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
Jennifer L HamadDepartment of Chemistry, Stanford University, Stanford, CA, USA; Department of Biology, Stanford University, Stanford, CA, USA.
Sean A Yamada-HunterCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA; Parker Institute for Cancer Immunotherapy, Stanford University School of Medicine, Stanford, CA, USA.
Louai LabaniehCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA; Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Elena SotilloCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA; Weill West Coast Cancer Hub, Stanford, CA, USA.
Crystal L MackallCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA; Weill West Coast Cancer Hub, Stanford, CA, USA; Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA; Parker Institute for Cancer Immunotherapy, Stanford University School of Medicine, Stanford, CA, USA; Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA; Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford University School of Medicine, Stanford, CA, USA. Electronic address: cmackall@stanford.edu.

Funding

Translational Oncology Research Program (Project-005)P30CA124435 · NCI · STANFORD UNIVERSITY · PI MICHAEL KENNEY · 2007 to 2026
$71.4M
Tumor microenvironment-dependent therapy resistanceP01CA217959 · NCI · CHILDREN'S HOSP OF PHILADELPHIA · PI JULIE R PARK · 2017 to 2026
$20.7M
Multimodal AI modeling of T cell therapies to predict patient response and nominate advanced cell design strategiesOT2OD038101 · OD · STANFORD UNIVERSITY · PI Olivier Gevaert, Zinaida Good · 2025 to 2026
$4.2M
Developing Safe and Effective GD2-CAR T Cell Therapy for Diffuse Midline GliomasR01CA263500 · NCI · STANFORD UNIVERSITY · PI MACKALL, CRYSTAL, MONJE-DEISSEROTH, MICHELLE · 2021 to 2025
$3.3M
Next Generation Immunotherapies for Pediatric CancersR35CA283888 · NCI · STANFORD UNIVERSITY · PI Crystal Mackall · 2024 to 2026
$2.8M
NCI NIH HHS P01 CA217959NCI NIH HHS P30 CA124435NCI NIH HHS R01 CA263500NCI NIH HHS R35 CA283888NIH HHS OT2 OD038101
6 · The paper itself

Abstract

We sought to endow T cell autonomous regulation of cell surface protein expression by exploiting the conditional proteolytic activity of ADAM17 following T cell activation. Screening of canonical ADAM17 substrates yielded a minimal 15-aa CD62L-derived motif that confers rapid and reversible cleavage of a receptor following T cell activation-termed activation-induced release (AIR). Embedding AIR into tonic-signaling CARs reduced basal CAR expression proportional to the degree of tonic signaling induced, curtailing exhaustion and improving antitumor potency. In non-tonic signaling CARs, AIR decreased activation-induced cell death and enhanced T cell expansion after stimulation. AIR's modularity supports higher-order logic-gating; AIR-regulated peptide masks enable antigen-dependent unmasking of an EGFR-targeting CAR. Finally, CRISPR knockin of AIR into endogenous FAS or TGFBR2 endowed them with activation-induced shedding, which enhanced tumor clearance while preserving signaling in non-activating conditions. AIR is a compact switch that provides fast, autonomous regulation of surface proteins for next-generation cell therapies.

Indexed as

ADAM17 ProteinReceptors, Antigen, T-CellReceptors, Chimeric AntigenAnimalsHumansLymphocyte ActivationMiceProteolysisSignal TransductionT-LymphocytesADAM17 ProteinADAM17 protein, humanReceptors, Antigen, T-CellReceptors, Chimeric AntigenADAM17bioengineeringcancerCARimmunotherapyproteasesynthetic biologyT cells

Identifiers

PMID42143019
PMCPMC13286248

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.