Evidence map›Paper›PMID 31736230›Full record

ArticleMolecular oncology2020

TR1801-ADC: a highly potent cMet antibody-drug conjugate with high activity in patient-derived xenograft models of solid tumors.

Marco Gymnopoulos, Oscar Betancourt, Vincent Blot, Ryo Fujita, Diana Galvan, Vincent Lieuw, Sophie Nguyen, Jeanette Snedden, Christine Stewart, Jose Villicana and 11 more

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

Article in Molecular oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed, 1 pooled it
3.5field-weighted citation impact, top 6% 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

39 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.

  1. Pooled it
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  14. The MET Oncogene: An Update on Targeting Strategies.Pharmaceuticals (Basel, Switzerland) · 2024
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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

21 authors at 2 institutions in 2 countries.

Marco GymnopoulosTanabe Research Laboratories U.S.A., Inc., San Diego, CA, USA.ORCID 0000-0001-6885-5951
Oscar BetancourtTanabe Research Laboratories U.S.A., Inc., San Diego, CA, USA.
Vincent BlotTanabe Research Laboratories U.S.A., Inc., San Diego, CA, USA.
Ryo FujitaTanabe Research Laboratories U.S.A., Inc., San Diego, CA, USA.
Diana GalvanTanabe Research Laboratories U.S.A., Inc., San Diego, CA, USA.
Vincent LieuwTanabe Research Laboratories U.S.A., Inc., San Diego, CA, USA.
Sophie NguyenTanabe Research Laboratories U.S.A., Inc., San Diego, CA, USA.
Jeanette SneddenTanabe Research Laboratories U.S.A., Inc., San Diego, CA, USA.
Christine StewartTanabe Research Laboratories U.S.A., Inc., San Diego, CA, USA.
Jose VillicanaTanabe Research Laboratories U.S.A., Inc., San Diego, CA, USA.
Jon WojciakTanabe Research Laboratories U.S.A., Inc., San Diego, CA, USA.
Eley WongTanabe Research Laboratories U.S.A., Inc., San Diego, CA, USA.
Raul PardoSpirogen, a member of the AstraZeneca Group, London, UK.
Neki PatelSpirogen, a member of the AstraZeneca Group, London, UK.
Francois D'HoogeSpirogen, a member of the AstraZeneca Group, London, UK.
Balakumar VijayakrishnanSpirogen, a member of the AstraZeneca Group, London, UK.
Conor BarrySpirogen, a member of the AstraZeneca Group, London, UK.
John A HartleySpirogen, a member of the AstraZeneca Group, London, UK.
Philip W HowardSpirogen, a member of the AstraZeneca Group, London, UK.
Roland NewmanTanabe Research Laboratories U.S.A., Inc., San Diego, CA, USA.
Julia CoronellaTanabe Research Laboratories U.S.A., Inc., San Diego, CA, USA.
Tanabe Research Laboratories · USAstraZeneca (United Kingdom) · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

cMet is a well-characterized oncogene that is the target of many drugs including small molecule and biologic pathway inhibitors, and, more recently, antibody-drug conjugates (ADCs). However, the clinical benefit from cMet-targeted therapy has been limited. We developed a novel cMet-targeted 'third-generation' ADC, TR1801-ADC, that was optimized at different levels including specificity, stability, toxin-linker, conjugation site, and in vivo efficacy. Our nonagonistic cMet antibody was site-specifically conjugated to the pyrrolobenzodiazepine (PBD) toxin-linker tesirine and has picomolar activity in cancer cell lines derived from different solid tumors including lung, colorectal, and gastric cancers. The potency of our cMet ADC is independent of MET gene copy number, and its antitumor activity was high not only in high cMet-expressing cell lines but also in medium-to-low cMet cell lines (40 000-90 000 cMet/cell) in which a cMet ADC with tubulin inhibitor payload was considerably less potent. In vivo xenografts with low-medium cMet expression were also very responsive to TR1801-ADC at a single dose, while a cMet ADC using a tubulin inhibitor showed a substantially reduced efficacy. Furthermore, TR1801-ADC had excellent efficacy with significant antitumor activity in 90% of tested patient-derived xenograft models of gastric, colorectal, and head and neck cancers: 7 of 10 gastric models, 4 of 10 colorectal cancer models, and 3 of 10 head and neck cancer models showed complete tumor regression after a single-dose administration. Altogether, TR1801-ADC is a new generation cMet ADC with best-in-class preclinical efficacy and good tolerability in rats.

Indexed as

AnimalsAntineoplastic AgentsBenzodiazepinesBiliary Tract NeoplasmsCell Line, TumorColonic NeoplasmsFemaleGene Expression Regulation, NeoplasticHead and Neck NeoplasmsHumansImmunoconjugatesMaleMiceMice, Inbred BALB CMice, NudeNeoplasmsAntineoplastic AgentsBenzodiazepinesImmunoconjugatesMET protein, humanProto-Oncogene Proteins c-metPyrrolespyrrolo(2,1-c)(1,4)benzodiazepineantibodycMetdrug conjugategastrointestinal cancerpyrrolobenzodiazepinesolid tumors

Identifiers

PMID31736230
PMCPMC6944112
OpenAlexW2987115036

What OpenQuestion holds

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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.