Evidence map›Paper›PMID 24947019›Full record

ArticleLeukemia2015

Tumor antigen ROR1 targeted drug delivery mediated selective leukemic but not normal B-cell cytotoxicity in chronic lymphocytic leukemia.

R Mani, Y Mao, F W Frissora, C-L Chiang, J Wang, Y Zhao, Y Wu, B Yu, R Yan, X Mo and 12 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Leukemia, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed, 2 pooled it
2.7field-weighted citation impact, top 10% 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

34 citing papers in PubMed, 2 syntheses or guidelines pooled it, 44 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Targeting PP2A in cancer: an underrated option.Journal of experimental & clinical cancer research : CR · 2025
    Review
  4. Review
  5. Review
  6. Article
  7. Article
  8. Review
  9. Pharmacological Effects of FTY720 and its Derivatives.Current topics in medicinal chemistry · 2024
    Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Review
  20. Observational
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

22 authors at 3 institutions in 1 country.

R Mani1] Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH, USA [2] Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA [3] Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA.
Y Mao1] Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA [2] Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH, USA [3] Center for Affordable Nanoengineering of Polymeric Biomedical Devices, The Ohio State University, Columbus, OH, USA.
F W Frissora1] Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH, USA [2] Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
C-L Chiang1] Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH, USA [2] Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
J WangComprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
Y ZhaoDivision of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH, USA.
Y WuCenter for Affordable Nanoengineering of Polymeric Biomedical Devices, The Ohio State University, Columbus, OH, USA.
B Yu1] Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA [2] Center for Affordable Nanoengineering of Polymeric Biomedical Devices, The Ohio State University, Columbus, OH, USA.
R YanDivision of Medicinal Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH, USA.
X MoCenter for Biostatistics, The Ohio State University, Columbus, OH, USA.
L YuCenter for Biostatistics, The Ohio State University, Columbus, OH, USA.
J FlynnDivision of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH, USA.
J JonesDivision of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH, USA.
L AndritsosDivision of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH, USA.
S BaskarPediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
C RaderDepartment of Cancer Biology and Department of Molecular Therapeutics, The Scripps Research Institute, Scripps Florida, Jupiter, FL, USA.
M A Phelps1] Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA [2] Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH, USA.
C-S Chen1] Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA [2] Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA [3] Division of Medicinal Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH, USA.
R J Lee1] Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA [2] Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH, USA [3] Center for Affordable Nanoengineering of Polymeric Biomedical Devices, The Ohio State University, Columbus, OH, USA.
J C Byrd1] Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH, USA [2] Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA [3] Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA [4] Division of Medicinal Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH, USA.
L J Lee1] Center for Affordable Nanoengineering of Polymeric Biomedical Devices, The Ohio State University, Columbus, OH, USA [2] Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH, USA.
N Muthusamy1] Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH, USA [2] Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA [3] Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA.
The Ohio State University · USCenter for Cancer Research · USScripps Research Institute · US

Funding

Tissue CoreP01CA081534 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KIPPS, THOMAS J · 2000 to 2016
$59.5M
TWO SIGNAL REQUIREMENT FOR NATURAL KILLER IMMUNITYP01CA095426 · NCI · OHIO STATE UNIVERSITY · PI CALIGIURI, MICHAEL A · 2002 to 2016
$29.6M
SPORE Leukemia Tissue BankP50CA140158 · NCI · OHIO STATE UNIVERSITY · PI BLOOMFIELD, CLARA D · 2009 to 2013
$11.2M
Novel Enediyne-Based Antibody-Drug Conjugates for CancersR01CA204484 · NCI · UNIVERSITY OF FLORIDA · PI Natarajan Muthusamy, Ben Shen · 2017 to 2026
$4.6M
Validation of microRNAs as therapeutic targets in hematological malignanciesR01CA135332 · NCI · OHIO STATE UNIVERSITY · PI MARCUCCI, GUIDO, MUTHUSAMY, NATARAJAN · 2011 to 2015
$1.6M
Novel Immunotherapies for Lymphoid MalignanciesR01CA159296 · NCI · OHIO STATE UNIVERSITY · PI BYRD, JOHN C., MUTHUSAMY, NATARAJAN · 2012 to 2016
$1.6M
NCI NIH HHS NCI-P50-CA140158NCI NIH HHS P01 CA081534NCI NIH HHS P01 CA095426NCI NIH HHS P50 CA140158NCI NIH HHS R01 CA135332NCI NIH HHS R01 CA159296NCI NIH HHS R01 CA204484
6 · The paper itself

Abstract

Selective cytotoxicity to cancer cells without compromising their normal counterparts pose a huge challenge for traditional drug design. Here we developed a tumor antigen-targeted delivery of immunonanoparticle carrying a novel non-immunosuppressive FTY720 derivative OSU-2S with potent cytotoxicity against leukemic B cells. OSU-2S induces activation of protein phosphatase 2A (PP2A), phosphorylation and nuclear translocation of SHP1(S591) and deregulation of multiple cellular processes in chronic lymphocytic leukemia (CLL) resulting in potent cytotoxicity. To preclude OSU-2S-mediated effects on these ubiquitous phosphatases in unintended cells and avoid potential adverse effects, we developed an OSU-2S-targeted delivery of immunonanoparticles (2A2-OSU-2S-ILP), that mediated selective cytotoxicity of CLL but not normal B cells through targeting receptor tyrosine kinase ROR1 expressed in leukemic but not normal B cells. Developing a novel spontaneous CLL mouse model expressing human ROR1 (hROR1) in all leukemic B cells, we demonstrate the therapeutic benefit of enhanced survival with 2A2-OSU-2S-ILP in vivo. The newly developed non-immunosuppressive OSU-2S, its delivery using human CLL directed immunonanoparticles and the novel transgenic (Tg) mouse model of CLL that expresses hROR1 exclusively in leukemic B cell surface are highly innovative and can be applied to CLL and other ROR1+ malignancies including mantle cell lymphoma and acute lymphoblastic leukemia.

Indexed as

Drug Delivery SystemsAnimalsApoptosisB-LymphocytesCell Line, TumorCell SurvivalFingolimod HydrochlorideHumansImmunosuppressive AgentsLeukemia, Lymphocytic, Chronic, B-CellLiposomesLymphoma, Mantle-CellMiceMice, TransgenicNanoparticlesOligonucleotide Array Sequence AnalysisFingolimod HydrochlorideImmunosuppressive AgentsLiposomesPropylene GlycolsProtein Kinase CReceptor Tyrosine Kinase-like Orphan ReceptorsROR1 protein, humanSphingosine

Identifiers

PMID24947019
PMCPMC4272672
OpenAlexW2096374380

What OpenQuestion holds

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Registered trials

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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.