Evidence map›Paper›PMID 41449802›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2026

Rational redesign of antigen binding domain improves in vivo efficacy of the CD22-CAR.

Kole R DeGolier, Catherine Pham-Danis, Samuel D Burciaga, Zachary H Walsh, Christine Brzezinski, Amanda J Novak, Lillie Leach, Jennifer Cimons, Wei Li, Zhu Zhongyu and 4 more

Abstract read
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In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. 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.

Kole R DeGolierDepartment of Immunology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Immunology and Genomic Medicine, National Jewish Health, Denver, CO 80206, USA.
Catherine Pham-DanisDepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Samuel D BurciagaDepartment of Immunology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Zachary H WalshDepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Christine BrzezinskiDepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Amanda J NovakDepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Lillie LeachDepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Jennifer CimonsDepartment of Immunology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Wei LiDivision of Infectious Diseases, Department of Medicine, University of Pittsburgh Medical School, Pittsburgh, PA 15213, USA.
Zhu ZhongyuNational Cancer Institute, National Institutes of Health, Bethesda, MD 20814, USA.
Dimiter DimitrovDivision of Infectious Diseases, Department of Medicine, University of Pittsburgh Medical School, Pittsburgh, PA 15213, USA.
James P Scott-BrowneDepartment of Immunology and Genomic Medicine, National Jewish Health, Denver, CO 80206, USA.
M Eric KohlerDepartment of Immunology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Center for Cancer and Blood Disorders, Children's Hospital Colorado, Aurora, CO 80045, USA.
Terry J FryDepartment of Immunology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Center for Cancer and Blood Disorders, Children's Hospital Colorado, Aurora, CO 80045, USA. Electronic address: terry.fry@cuanschutz.edu.

Funding

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
NCI NIH HHS U01 CA232486
6 · The paper itself

Abstract

Chimeric antigen receptor (CAR) T cells targeting CD19 are highly effective against B lineage malignancies. However, about half of patients either fail to achieve complete remission (in the case of lymphoma) or they relapse (in the case of acute lymphoblastic leukemia). CD22 represents an alternative highly B lineage-restricted target. Although CD22-targeted CAR-T cells are clinically active, targeting this antigen has proven difficult relative to CD19, attributable, in part, to lower expression levels. Commonly, patients relapse or progress with reduced CD22 expression compared to pre-treatment, contrasting with the loss of CD19 expression typically observed after CD19-CAR therapy. Prior work demonstrated that an antigen-independent "tonic" signaling CD22-CAR has enhanced clinical efficacy relative to other CD22-CARs tested. However, tonic signaling has been shown to be detrimental to long-term CAR-T cell function. Here, we demonstrate a balance between binding affinity and antigen-independent signaling (determined by length of the linker between fragment variable regions) in determining CAR function against CD22. We show that CAR function against both CD22

Indexed as

Immunotherapy, AdoptiveReceptors, Chimeric AntigenSialic Acid Binding Ig-like Lectin 2AnimalsAntigens, CD19Cell Line, TumorHumansMicePrecursor Cell Lymphoblastic Leukemia-LymphomaProtein BindingProtein DomainsSignal TransductionT-LymphocytesXenograft Model Antitumor AssaysAntigens, CD19CD22 protein, humanReceptors, Chimeric AntigenSialic Acid Binding Ig-like Lectin 2acute lymphoblastic leukemiaaffinityCAR-T cellsCD22cellular immunotherapyLeukemiatonic signaling

Identifiers

PMID41449802
PMCPMC12866949

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.