Evidence map›Paper›PMID 28087047›Full record

ArticleCellular immunology2017

Rational design of low immunogenic anti CD25 recombinant immunotoxin for T cell malignancies by elimination of T cell epitopes in PE38.

Ronit Mazor, Gilad Kaplan, Dong Park, Youjin Jang, Fred Lee, Robert Kreitman, Ira Pastan

Abstract read
In one paragraph

Article in Cellular immunology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.9field-weighted citation impact, top 15% 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

15 citing papers in PubMed, 23 citations in OpenAlex.

  1. Bacterial exotoxins in medicine: potential value and perspectives.International journal of medical sciences · 2025
    Review
  2. Frontiers in oncology · 2022
    Review
  3. Bacteria-Based Cancer Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021
    Review
  4. Immunogenicity Challenges Associated with Subcutaneous Delivery of Therapeutic Proteins.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2021
    Review
  5. Immunogenicity of Immunotoxins ContainingFrontiers in immunology · 2020
    Review
  6. Review
  7. Immunogenicity of Protein Pharmaceuticals.Journal of pharmaceutical sciences · 2019
    Review
  8. Article
  9. Review
  10. Improving theMolecular cancer therapeutics · 2018
    Article
  11. Review
  12. Domain II ofToxins · 2018
    Article
  13. Review
  14. Article
  15. 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

7 authors at 2 institutions in 1 country.

Ronit MazorLaboratory of Molecular Biology, Center for Cancer Research, National Institutes of Health, Bethesda, MD 20892-4264, USA. Electronic address: mazorr@mail.nih.gov.
Gilad KaplanLaboratory of Molecular Biology, Center for Cancer Research, National Institutes of Health, Bethesda, MD 20892-4264, USA. Electronic address: kaplang@medimmune.com.
Dong ParkLaboratory of Molecular Biology, Center for Cancer Research, National Institutes of Health, Bethesda, MD 20892-4264, USA. Electronic address: Parkkoon77@gmail.com.
Youjin JangLaboratory of Molecular Biology, Center for Cancer Research, National Institutes of Health, Bethesda, MD 20892-4264, USA. Electronic address: yjj8817@gmail.com.
Fred LeeLaboratory of Molecular Biology, Center for Cancer Research, National Institutes of Health, Bethesda, MD 20892-4264, USA. Electronic address: fred.lee@nih.gov.
Robert KreitmanLaboratory of Molecular Biology, Center for Cancer Research, National Institutes of Health, Bethesda, MD 20892-4264, USA. Electronic address: kreitmar@mail.nih.gov.
Ira PastanLaboratory of Molecular Biology, Center for Cancer Research, National Institutes of Health, Bethesda, MD 20892-4264, USA. Electronic address: pastani@mail.nih.gov.
Center for Cancer Research · USNational Institutes of Health · US

Funding

Immunotoxin Therapy of Solid and Hematopoietic Tumors: Preclinical StudiesZIABC008753 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI PASTAN, IRA · 2009 to 2024
$33.1M
Development of Recombinant Toxins to Treat Hematologic MalignanciesZIABC010301 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI KREITMAN, ROBERT · 2009 to 2025
$21.7M
IMMUNOTOXIN THERAPY OF SOLID AND HEMATOPOIETIC TUMORS: PRECLINICAL STUDIESZ01BC008753 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI PASTAN, IRA · 1996 to 2008
$3.2M
Intramural NIH HHS Z01 BC008753
6 · The paper itself

Abstract

LMB-2, is a potent recombinant immunotoxin (RIT) that is composed of scFv antibody that targets CD25 (Tac) and a toxin fragment (PE38). It is used to treat T cell leukemias and lymphomas. To make LMB-2 less immunogenic, we introduced a large deletion in domain II and six point mutations in domain III that were previously shown to reduce T cell activation in other RITs. We found that unlike other RITs, deletion of domain II from LMB-2 severely compromised its activity. Rather than deletion, we identified T cell epitopes in domain II and used alanine substitutions to identify point mutations that diminished those epitopes. The novel RIT, LMB-142 contains a 38kDa toxin and nine point mutations that diminished T cell response to the corresponding peptides by an average of 75%. LMB-142 has good cytotoxic activity and has lower nonspecific toxicity in mice. LMB-142 should be more efficient in cancer therapy because more treatment cycles can be given.

Indexed as

AnimalsAntibodies, MonoclonalBacterial ToxinsCell Line, TumorCell ProliferationCytokinesDrug DesignEnzyme-Linked Immunospot AssayEpitopes, T-LymphocyteExotoxinsFemaleGenetic EngineeringHumansImmunotherapyImmunotoxinsInterleukin-2 Receptor alpha SubunitAntibodies, MonoclonalB3(Fv)-PE38KDEL recombinant immunotoxinBacterial ToxinsCytokinesEpitopes, T-LymphocyteExotoxinsImmunotoxinsInterleukin-2 Receptor alpha SubunitDeimmunizationDomain IIIL2 receptorImmunogenicityPseudomonas exotoxin ARITTACT cell epitopes

Identifiers

PMID28087047
PMCPMC5344129
OpenAlexW2569284105

What OpenQuestion holds

Textmetadata
LicenceTDM
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.