Evidence map›Paper›PMID 28544589›Full record

ArticleCancer medicine2017

Methionine tumor starvation by erythrocyte-encapsulated methionine gamma-lyase activity controlled with per os vitamin B6.

Fabien Gay, Karine Aguera, Karine Sénéchal, Angie Tainturier, Willy Berlier, Delphine Maucort-Boulch, Jérôme Honnorat, Françoise Horand, Yann Godfrin, Vanessa Bourgeaux

Open access · goldAbstract read
In one paragraph

Article in Cancer medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 1 pooled it
2.6field-weighted citation impact, top 12% 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

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

  1. Pooled it
  2. Review
  3. Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. Article
  10. Glioblastoma and Methionine Addiction.International journal of molecular sciences · 2022
    Review
  11. Targeting the methionine addiction of cancer.American journal of cancer research · 2022
    Review
  12. L-Lysine α-Oxidase: Enzyme with Anticancer Properties.Pharmaceuticals (Basel, Switzerland) · 2021
    Review
  13. Nucleic Acid Delivery with Red-Blood-Cell-Based Carriers.International journal of molecular sciences · 2021
    Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. Review
  19. Article
  20. Enzymes in Metabolic Anticancer Therapy.Advances in experimental medicine and biology · 2019
    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

10 authors at 3 institutions in 1 country.

Fabien GayERYTECH Pharma, Lyon, France.ORCID http://orcid.org/0000-0002-0897-7313
Karine AgueraERYTECH Pharma, Lyon, France.
Karine SénéchalERYTECH Pharma, Lyon, France.
Angie TainturierVoxcan, Marcy l'Etoile, France.
Willy BerlierERYTECH Pharma, Lyon, France.
Delphine Maucort-BoulchService de Biostatistique, Hospices Civils de Lyon, Lyon, France.
Jérôme HonnoratUniversité Claude Bernard Lyon 1, Villeurbanne, France.
Françoise HorandERYTECH Pharma, Lyon, France.
Yann GodfrinERYTECH Pharma, Lyon, France.
Vanessa BourgeauxERYTECH Pharma, Lyon, France.
Erytech Pharma (France) · FRUniversité Claude Bernard Lyon 1 · FRVetAgro Sup · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Erymet is a new therapy resulting from the encapsulation of a methionine gamma-lyase (MGL; EC number 4.4.1.11) in red blood cells (RBC). The aim of this study was to evaluate erymet potential efficacy in methionine (Met)-dependent cancers. We produced a highly purified MGL using a cGMP process, determined the pharmacokinetics/pharmacodynamics (PK/PD) properties of erymet in mice, and assessed its efficacy on tumor growth prevention. Cytotoxicity of purified MGL was tested in six cancer cell lines. CD1 mice were injected with single erymet product supplemented or not with vitamin B6 vitamer pyridoxine (PN; a precursor of PLP cofactor). NMRI nude mice were xenografted in the flank with U-87 MG-luc2 glioblastoma cells for tumor growth study following five intravenous (IV) injections of erymet with daily PN oral administration. Endpoints included efficacy and event-free survival (EFS). Finally, a repeated dose toxicity study of erymet combined with PN cofactor was conducted in CD1 mice. Recombinant MGL was cytotoxic on 4/6 cell lines tested. MGL half-life was increased from <24 h to 9-12 days when encapsulated in RBC. Conversion of PN into PLP by RBC was demonstrated. Combined erymet + PN treatment led to a sustained Met depletion in plasma for several days with a 85% reduction of tumor volume after 45 days following cells implantation, and a significant EFS prolongation for treated mice. Repeated injections in mice exhibited a very good tolerability with only minor impact on clinical state (piloerection, lean aspect) and a slight decrease in hemoglobin and triglyceride concentrations. This study demonstrated that encapsulation of methioninase inside erythrocyte greatly enhanced pharmacokinetics properties of the enzyme and is efficacy against tumor growth. The perspective on these results is the clinical evaluation of the erymet product in patients with Met starvation-sensitive tumors.

Indexed as

Drug Delivery SystemsErythrocytesAnimalsAntineoplastic AgentsCarbon-Sulfur LyasesCell Line, TumorCell ProliferationCell SurvivalHumansMaleMethionineMice, NudeNeoplasmsPyridoxal PhosphatePyridoxineRecombinant ProteinsAntineoplastic AgentsCarbon-Sulfur LyasesL-methionine gamma-lyaseMethioninePyridoxal PhosphatePyridoxineRecombinant ProteinsErymetmethionine-dependent cancersmethionine gamma-lyasepyridoxal 5′-phosphatered blood cells

Identifiers

PMID28544589
PMCPMC5463067
OpenAlexW2620007230

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.