Evidence map›Paper›PMID 35560156›Full record

ArticleBlood2022

Cytosine base editing enables quadruple-edited allogeneic CART cells for T-ALL.

Caroline Diorio, Ryan Murray, Mark Naniong, Luis Barrera, Adam Camblin, John Chukinas, Lindsey Coholan, Aaron Edwards, Tori Fuller, Claudia Gonzales and 17 more

Open access · hybridAbstract read
In one paragraph

Article in Blood, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.

0numbers the graph read from it
0cells of the map it votes in
89citing papers in PubMed
9.9field-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

89 citing papers in PubMed, 122 citations in OpenAlex.

  1. Review
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  4. In vivo base editing of Asgr1 reduces blood lipids in mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
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29 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

27 authors at 2 institutions in 1 country.

Caroline DiorioDivision of Oncology, Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA.ORCID 0000-0002-8005-3836
Ryan MurrayBeam Therapeutics, Cambridge, MA.
Mark NaniongBeam Therapeutics, Cambridge, MA.
Luis BarreraBeam Therapeutics, Cambridge, MA.ORCID 0000-0003-0612-6416
Adam CamblinBeam Therapeutics, Cambridge, MA.
John ChukinasDivision of Oncology, Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA.
Lindsey CoholanBeam Therapeutics, Cambridge, MA.
Aaron EdwardsBeam Therapeutics, Cambridge, MA.
Tori FullerDivision of Oncology, Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA.
Claudia GonzalesBeam Therapeutics, Cambridge, MA.
Stephan A GruppDivision of Oncology, Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA.
Alden LaddBeam Therapeutics, Cambridge, MA.
Melissa LeBeam Therapeutics, Cambridge, MA.
Angelica MessanaBeam Therapeutics, Cambridge, MA.ORCID 0000-0002-3484-416X
Faith MusengeBeam Therapeutics, Cambridge, MA.ORCID 0000-0002-4209-598X
Haley NewmanDivision of Oncology, Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA.ORCID 0000-0002-3022-8052
Yeh-Chuin PohBeam Therapeutics, Cambridge, MA.ORCID 0000-0003-3510-6369
Henry PoulinBeam Therapeutics, Cambridge, MA.
Theresa RyanDivision of Oncology, Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA.
Rawan ShraimDivision of Oncology, Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA.
Sarah K TasianDivision of Oncology, Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA.ORCID 0000-0003-1327-1662
Tiffaney VincentDivision of Oncology, Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA.
Lauren YoungBeam Therapeutics, Cambridge, MA.
Yingying ZhangBeam Therapeutics, Cambridge, MA.
Giuseppe CiaramellaBeam Therapeutics, Cambridge, MA.ORCID 0000-0003-3339-7211
Jason GehrkeBeam Therapeutics, Cambridge, MA.
David T TeacheyDivision of Oncology, Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA.ORCID 0000-0001-7373-8987
Beam Therapeutics (United States) · USChildren's Hospital of Philadelphia · US

Funding

CANCER RESEARCH TRAINING PROGRAMT32CA009615 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Gregory L Beatty, MICHAEL D HOGARTY · 1988 to 2026
$10.4M
Improving risk allocation and developing novel therapies for children with T-ALL and T-LLR01CA193776 · NCI · CHILDREN'S HOSP OF PHILADELPHIA · PI Terzah M Horton, ADAM B OLSHEN · 2015 to 2026
$6.2M
COG NCTN Integrated Translational Science Center for Hematopoietic Malignancies in ChildrenUG1CA233249 · NCI · PUBLIC HEALTH INSTITUTE · PI MESHINCHI, SOHEIL · 2019 to 2025
$4.9M
Multispecific targeting incorporating cytokine receptor pathways in high risk pediatric acute leukemias to improve durability of adoptive cell therapy-induced remissionsU01CA232486 · NCI · UNIVERSITY OF COLORADO DENVER · PI FRY, TERRY J., TASIAN, SARAH KATHLEEN · 2018 to 2018
$4.0M
Biomarkers of dasatinib response and resistance in T-cell acute lymphoblastic leukemiaR01CA264837 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI TEACHEY, DAVID T., YANG, JUN J. · 2021 to 2025
$3.0M
Towards rational design of combination therapeutic targetsU01CA243072 · NCI · CHILDREN'S HOSP OF PHILADELPHIA · PI TAN, KAI, TASIAN, SARAH KATHLEEN · 2020 to 2024
$2.6M
Genomic Profiling of T-cell Acute Lymphoblastic Leukemia in ChildrenR03CA256550 · NCI · CHILDREN'S HOSP OF PHILADELPHIA · PI MULLIGHAN, CHARLES G., TEACHEY, DAVID T. · 2021 to 2021
$382k
NCI NIH HHS R01 CA193776NCI NIH HHS R01 CA264837NCI NIH HHS R03 CA256550NCI NIH HHS T32 CA009615NCI NIH HHS U01 CA232486NCI NIH HHS U01 CA243072NCI NIH HHS UG1 CA233249
6 · The paper itself

Abstract

Allogeneic chimeric antigen receptor T-cell (CART) therapies require multiple gene edits to be clinically tractable. Most allogeneic CARTs have been created using gene editing techniques that induce DNA double-stranded breaks (DSBs), resulting in unintended on-target editing outcomes with potentially unforeseen consequences. Cytosine base editors (CBEs) install C•G to T•A point mutations in T cells, with between 90% and 99% efficiency to silence gene expression without creating DSBs, greatly reducing or eliminating undesired editing outcomes following multiplexed editing as compared with clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9). Using CBE, we developed 7CAR8, a CD7-directed allogeneic CART created using 4 simultaneous base edits. We show that CBE, unlike CRISPR-Cas9, does not impact T-cell proliferation, lead to aberrant DNA damage response pathway activation, or result in karyotypic abnormalities following multiplexed editing. We demonstrate 7CAR8 to be highly efficacious against T-cell acute lymphoblastic leukemia (T-ALL) using multiple in vitro and in vivo models. Thus, CBE is a promising technology for applications requiring multiplexed gene editing and can be used to manufacture quadruple-edited 7CAR8 cells, with high potential for clinical translation for relapsed and refractory T-ALL.

Indexed as

Hematopoietic Stem Cell TransplantationPrecursor T-Cell Lymphoblastic Leukemia-LymphomaCRISPR-Cas SystemsCytosineGene EditingHumansCytosine

Identifiers

PMID35560156
PMCPMC9373016
OpenAlexW4280491484

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.