Evidence map›Paper›PMID 30850736›Full record

ArticleLeukemia2019

A fully human anti-IL-7Rα antibody promotes antitumor activity against T-cell acute lymphoblastic leukemia.

Padma Akkapeddi, Rita Fragoso, Julie A Hixon, Ana Sofia Ramalho, Mariana L Oliveira, Tânia Carvalho, Andreas Gloger, Mattia Matasci, Francisco Corzana, Scott K Durum and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in Leukemia, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed, 1 pooled it
7.3field-weighted citation impact, top 3% 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

38 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. A Complementarity-Based Approach to De Novo Binder Design.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  9. Review
  10. Review
  11. Article
  12. Review
  13. Review
  14. Review
  15. Review
  16. Notch Partners in the Long Journey of T-ALL Pathogenesis.International journal of molecular sciences · 2023
    Review
  17. Review
  18. Review
  19. The Role of IL-7 and IL-7R in Cancer Pathophysiology and Immunotherapy.International journal of molecular sciences · 2022
    Review
  20. A Bright Horizon: Immunotherapy for Pediatric T-Cell Malignancies.International journal of molecular sciences · 2022
    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

13 authors at 6 institutions in 5 countries.

Padma AkkapeddiInstituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina da Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028, Lisboa, Portugal.
Rita FragosoInstituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina da Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028, Lisboa, Portugal.
Julie A HixonCytokines and Immunity Section, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA.
Ana Sofia RamalhoInstituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina da Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028, Lisboa, Portugal.
Mariana L OliveiraInstituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina da Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028, Lisboa, Portugal.
Tânia CarvalhoInstituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina da Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028, Lisboa, Portugal.
Andreas GlogerDepartamento de Química, Universidad de La Rioja, Centro de Investigación en Síntesis Química, 26006, Logroño, Spain.
Mattia MatasciPhilochem AG, Libernstrasse 3, Otelfingen, Switzerland.
Francisco CorzanaPhilochem AG, Libernstrasse 3, Otelfingen, Switzerland.
Scott K DurumCytokines and Immunity Section, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA.
Dario NeriDepartment of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH Zürich), Vladimir-Prelog-Weg 4, Zürich, Switzerland.
Gonçalo J L BernardesInstituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina da Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028, Lisboa, Portugal. gbernardes@medicina.ulisboa.pt.
João T BarataInstituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina da Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028, Lisboa, Portugal. joao_barata@medicina.ulisboa.pt.
University of Lisbon · PTCenter for Cancer Research · USPhilochem (Switzerland) · CHETH Zurich · CHUniversidad de La Rioja · ESUniversity of Cambridge · GB

Funding

Cytokines and T Cell DevelopmentZIABC009287 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI DURUM, SCOTT · 2009 to 2025
$15.5M
6 · The paper itself

Abstract

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological cancer for which treatment options often result in incomplete therapeutic efficacy and long-term side-effects. Interleukin 7 (IL-7) and its receptor IL-7Rα promote T-ALL development and mutational activation of IL-7Rα associates with very high risk in relapsed disease. Using combinatorial phage-display libraries and antibody reformatting, we generated a fully human IgG1 monoclonal antibody (named B12) against both wild-type and mutant human IL-7Rα, predicted to form a stable complex with IL-7Rα at a different site from IL-7. B12 impairs IL-7/IL-7R-mediated signaling, sensitizes T-ALL cells to treatment with dexamethasone and can induce cell death per se. The antibody also promotes antibody-dependent natural killer-mediated leukemia cytotoxicity in vitro and delays T-cell leukemia development in vivo, reducing tumor burden and promoting mouse survival. B12 is rapidly internalized and traffics to the lysosome, rendering it an attractive vehicle for targeted intracellular delivery of cytotoxic cargo. Consequently, we engineered a B12-MMAE antibody-drug conjugate and provide proof-of-concept evidence that it has increased leukemia cell killing abilities as compared with the naked antibody. Our studies serve as a stepping stone for the development of novel targeted therapies in T-ALL and other diseases where IL-7Rα has a pathological role.

Indexed as

AnimalsAntibodies, MonoclonalAntineoplastic AgentsCell LineHumansImmunoglobulin GInterleukin-7MicePrecursor T-Cell Lymphoblastic Leukemia-LymphomaReceptors, Interleukin-7Signal TransductionT-LymphocytesAntibodies, MonoclonalAntineoplastic AgentsImmunoglobulin GInterleukin-7interleukin-7 receptor, alpha chainReceptors, Interleukin-7

Identifiers

PMID30850736
PMCPMC6733707
OpenAlexW2922290452

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.