Evidence map›Paper›PMID 26898190›Full record

ArticleLeukemia2016

High-affinity FRβ-specific CAR T cells eradicate AML and normal myeloid lineage without HSC toxicity.

R C Lynn, Y Feng, K Schutsky, M Poussin, A Kalota, D S Dimitrov, D J Powell

Abstract read
In one paragraph

Article in Leukemia, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.

0numbers the graph read from it
0cells of the map it votes in
92citing papers in PubMed
6.6field-weighted citation impact, top 2% 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

92 citing papers in PubMed, 116 citations in OpenAlex.

  1. Advances inMolecular therapy. Nucleic acids · 2026
    Review
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  6. Rational redesign of antigen binding domain improves in vivo efficacy of the CD22-CAR.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  7. Article
  8. Review
  9. Review
  10. Article
  11. Review
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  14. Recent advances of CAR-T cells in acute myeloid leukemia.Therapeutic advances in hematology · 2025
    Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review

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

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

7 authors at 3 institutions in 1 country.

R C LynnOvarian Cancer Research Center, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Y FengProtein Interactions Section, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA.
K SchutskyOvarian Cancer Research Center, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
M PoussinOvarian Cancer Research Center, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
A KalotaDivision of Hematology and Oncology, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.
D S DimitrovProtein Interactions Section, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA.
D J PowellOvarian Cancer Research Center, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Cancer Research Center · USCenter for Cancer Research · USUniversity of Pennsylvania · US

Funding

Human Monoclonal Antibodies Against CancerZIABC010701 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI DIMITROV, DIMITER S · 2009 to 2017
$6.9M
A Universal Approach to Personalized Adoptive T cell Therapy of CancerR01CA168900 · NCI · UNIVERSITY OF PENNSYLVANIA · PI POWELL, DANIEL J. · 2012 to 2016
$1.6M
Training in Vaccine & Immune TherapeuticsT32AI070099 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI WEINER, DAVID B. · 2008 to 2012
$938k
NCI NIH HHS R01 CA168900NIAID NIH HHS T32 AI070099
6 · The paper itself

Abstract

Acute myeloid leukemia (AML) is an aggressive malignancy, and development of new treatments to prolong remissions is warranted. Chimeric antigen receptor (CAR) T-cell therapies appear promising but on-target, off-tumor recognition of antigen in healthy tissues remains a concern. Here we isolated a high-affinity (HA) folate receptor beta (FRβ)-specific single-chain variable fragment (2.48 nm KD) for optimization of FRβ-redirected CAR T-cell therapy for AML. T cells stably expressing the HA-FRβ CAR exhibited greatly enhanced antitumor activity against FRβ(+) AML in vitro and in vivo compared with a low-affinity FRβ CAR (54.3 nm KD). Using the HA-FRβ immunoglobulin G, FRβ expression was detectable in myeloid-lineage hematopoietic cells; however, expression in CD34(+) hematopoietic stem cells (HSCs) was nearly undetectable. Accordingly, HA-FRβ CAR T cells lysed mature CD14(+) monocytes, while HSC colony formation was unaffected. Because of the potential for elimination of mature myeloid lineage, mRNA CAR electroporation for transient CAR expression was evaluated. mRNA-electroporated HA-FRβ CAR T cells retained effective antitumor activity in vitro and in vivo. Together, our results highlight the importance of antibody affinity in target protein detection and CAR development and suggest that transient delivery of potent HA-FRβ CAR T cells is highly effective against AML and reduces the risk for long-term myeloid toxicity.

Indexed as

AnimalsCell LineCell LineageFolate Receptor 2Hematopoietic Stem CellsHumansLeukemia, Myeloid, AcuteMiceMice, TransgenicMonocytesMyeloid CellsReceptors, Antigen, T-CellSingle-Chain AntibodiesT-LymphocytesFolate Receptor 2FOLR2 protein, humanReceptors, Antigen, T-CellSingle-Chain Antibodies

Identifiers

PMID26898190
PMCPMC4889499
OpenAlexW2288029921

What OpenQuestion holds

Textmetadata
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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.