Evidence map›Paper›PMID 41276526›Full record

ArticleNature communications2025

Multiplex gene-editing strategy to engineer allogeneic EGFR-targeting CAR T-cells with improved efficacy against solid tumors.

Ryan Murray, Md Raihan Chowdhury, Nuria Roxana Botticello-Romero, Kashvi Desai, Shanmuga Reddy Chilakapati, Brian Chong, Yixue Xia, Angelica Messana, Hanna Sobon, Joe Rocha and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Review
  6. Review
  7. Review
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

16 authors.

Ryan MurrayNew England Inflammation and Tissue Protection Institute, Department of Pharmaceutical Sciences, Bouvè College of Health Sciences, Northeastern University, Boston, MA, USA.
Md Raihan ChowdhuryNew England Inflammation and Tissue Protection Institute, Department of Pharmaceutical Sciences, Bouvè College of Health Sciences, Northeastern University, Boston, MA, USA.ORCID http://orcid.org/0000-0003-1085-1258
Nuria Roxana Botticello-RomeroNew England Inflammation and Tissue Protection Institute, Department of Pharmaceutical Sciences, Bouvè College of Health Sciences, Northeastern University, Boston, MA, USA.ORCID http://orcid.org/0009-0009-5866-177X
Kashvi DesaiNew England Inflammation and Tissue Protection Institute, Department of Pharmaceutical Sciences, Bouvè College of Health Sciences, Northeastern University, Boston, MA, USA.
Shanmuga Reddy ChilakapatiNew England Inflammation and Tissue Protection Institute, Department of Pharmaceutical Sciences, Bouvè College of Health Sciences, Northeastern University, Boston, MA, USA.
Brian ChongNew England Inflammation and Tissue Protection Institute, Department of Pharmaceutical Sciences, Bouvè College of Health Sciences, Northeastern University, Boston, MA, USA.ORCID http://orcid.org/0009-0009-3305-1131
Yixue XiaNew England Inflammation and Tissue Protection Institute, Department of Pharmaceutical Sciences, Bouvè College of Health Sciences, Northeastern University, Boston, MA, USA.
Angelica MessanaBeam Therapeutics, Cambridge, MA, USA.
Hanna SobonBeam Therapeutics, Cambridge, MA, USA.
Joe RochaBeam Therapeutics, Cambridge, MA, USA.
Faith MusengeBeam Therapeutics, Cambridge, MA, USA.
Adam CamblinBeam Therapeutics, Cambridge, MA, USA.
Giuseppe CiaramellaBeam Therapeutics, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-3339-7211
Michail V SitkovskyNew England Inflammation and Tissue Protection Institute, Department of Pharmaceutical Sciences, Bouvè College of Health Sciences, Northeastern University, Boston, MA, USA.
Colby R MaldiniBeam Therapeutics, Cambridge, MA, USA. cmaldini@wistar.org.ORCID http://orcid.org/0000-0002-5246-4187
Stephen M HatfieldNew England Inflammation and Tissue Protection Institute, Department of Pharmaceutical Sciences, Bouvè College of Health Sciences, Northeastern University, Boston, MA, USA. s.hatfield@northeastern.edu.ORCID http://orcid.org/0000-0002-2937-2268

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Chimeric Antigen Receptor (CAR) T cells have induced remarkable clinical responses in patients with hematological cancers. However, CAR T-cell therapies against solid tumors have not elicited similar outcomes since immunosuppressive barriers in the tumor microenvironment attenuate anti-tumor activity. Here, we describe a multifaceted approach to engineer allogeneic CAR T-cells resistant to both biochemical (hypoxia-adenosinergic) and immunological (PD-L1 and TGF-β) inhibitory signaling using an adenine base editor and a CRISPR-Cas12b nuclease. The resulting EGFR-targeting CAR T-cell product comprised a combination of six gene edits designed to evade allorejection (B2M, CIITA), prevent graft-versus-host disease (CD3E) and overcome biochemical (ADORA2A) and immunological (PDCD1, TGFBR2) barriers in solid tumor microenvironment of subcutaneously grown EGFR

Indexed as

Gene EditingImmunotherapy, AdoptiveLung NeoplasmsNeoplasmsReceptors, Chimeric AntigenT-LymphocytesAnimalsCell Line, TumorCRISPR-Cas SystemsErbB ReceptorsFemaleGraft vs Host DiseaseHumansMiceMice, Inbred NODReceptor, Transforming Growth Factor-beta Type IIEGFR protein, humanErbB ReceptorsReceptors, Chimeric AntigenReceptor, Transforming Growth Factor-beta Type II

Identifiers

PMID41276526
PMCPMC12749318

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.