Evidence map›Paper›PMID 31541350›Full record

ArticleTargeted oncology2019

Therapeutic Targeting of Golgi Phosphoprotein 2 (GOLPH2) with Armed Antibodies: A Preclinical Study of Anti-GOLPH2 Antibody Drug Conjugates in Lung and Colorectal Cancer Models of Patient Derived Xenografts (PDX).

Heike Liewen, Norbert Markuly, Heinz Läubli, Yang Liu, Matthias S Matter, Nora Liewen, Christoph Renner, Alfred Zippelius, Frank Stenner

Abstract read
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In one paragraph

Article in Targeted oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
1.2field-weighted citation impact, top 20% 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

2 citing papers in PubMed, 9 citations in OpenAlex.

  1. Review
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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

9 authors at 2 institutions in 2 countries.

Heike LiewenCureab GmbH, Benkenstrasse 254c, Technologiezentrum, 4108, Witterswil, Switzerland.
Norbert MarkulyCureab GmbH, Benkenstrasse 254c, Technologiezentrum, 4108, Witterswil, Switzerland.
Heinz LäubliMedical Oncology, University Hospital Basel & Laboratory Cancer Immunology, Department Biomedicine, University Basel, Petersgraben 4, 4031, Basel, Switzerland.
Yang LiuMedical Oncology, University Hospital Basel & Laboratory Cancer Immunology, Department Biomedicine, University Basel, Petersgraben 4, 4031, Basel, Switzerland.
Matthias S MatterInstitute of Pathology, University Hospital Basel, 4031, Basel, Switzerland.
Nora LiewenUniversity of Cologne, Albertus-Magnus-Platz, 50923, Cologne, Germany.
Christoph RennerMedical Oncology, University Hospital Basel & Laboratory Cancer Immunology, Department Biomedicine, University Basel, Petersgraben 4, 4031, Basel, Switzerland.
Alfred ZippeliusMedical Oncology, University Hospital Basel & Laboratory Cancer Immunology, Department Biomedicine, University Basel, Petersgraben 4, 4031, Basel, Switzerland.
Frank StennerMedical Oncology, University Hospital Basel & Laboratory Cancer Immunology, Department Biomedicine, University Basel, Petersgraben 4, 4031, Basel, Switzerland. frank.stenner@usb.ch.ORCID http://orcid.org/0000-0003-4541-8817
University Hospital of Basel · CHUniversity of Cologne · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundGolgi phosphoprotein 2 (GOLPH2) has been shown to be involved in chronic inflammatory processes and carcinogenesis. GOLPH2 is prominently overexpressed in hepatocellular carcinoma, melanoma, glioblastoma, prostate, lung, and colorectal cancer. With a low and tightly regulated expression in non-malignant tissues, GOLPH2 has been proposed as an attractive target for cancer therapy. However, GOLPH2 is predominantly located intracellularly and when situated outside of the cell it is proteolytically cleaved and shed from the cell surface. Until now, GOLPH2 has been regarded as an "undruggable" target.

objectiveWe sought to create antibodies that specifically bind to GOLPH2 overexpressing tumor cells. PATIENTS AND

methodsAntibodies binding to membranous GOLPH2 despite shedding of the protein were generated from a scFV library screening. These antibodies target the part of GOLPH2 that remains at the cell surface after proteolytic cleavage. These antibodies were then tested in vitro and in vivo.

resultsTwo candidates (G2-1 and G2-2) showed target specific binding in vitro. Utilizing a tumor array (n = 128 tumors) with G2-2 and a reference antibody, a GOLPH2 expression scoring system was established. Rapid internalization of the antibodies was noted so this was exploited to deliver a toxic payload of pyrrolobenzodiazepine (PBD). In two patient-derived xenograft (PDX)-models, colorectal and lung cancer, the G2-2 antibody drug conjugate (ADC) displayed high efficacy with significant tumor responses (P = 0.001; P = 0.013) and improved survival (P = 0.0001; P = 0.0011) compared with controls.

conclusionsTreatment with GOLPH2-directed antibodies induces durable responses in colorectal and lung cancer models. With a robust companion assay for GOLPH2 positivity at hand our findings prepare for the translation into a clinical trial.

Indexed as

AdenocarcinomaAnimalsAntineoplastic Agents, ImmunologicalColorectal NeoplasmsDisease Models, AnimalDrug Evaluation, PreclinicalGene Expression Regulation, NeoplasticGenetic EngineeringHCT116 CellsHeterograftsHumansImmunoconjugatesImmunotherapyLung NeoplasmsMembrane ProteinsMiceAntineoplastic Agents, ImmunologicalGOLM1 protein, humanImmunoconjugatesMembrane Proteins

Identifiers

PMID31541350
OpenAlexW2974448565

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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.