Evidence map›Paper›PMID 33302918›Full record

ArticleBMC cancer2020

A bispecific T cell engager targeting Glypican-1 redirects T cell cytolytic activity to kill prostate cancer cells.

Maria E Lund, Christopher B Howard, Kristofer J Thurecht, Douglas H Campbell, Stephen M Mahler, Bradley J Walsh

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
0.8field-weighted citation impact, top 28% 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

16 citing papers in PubMed, 19 citations in OpenAlex.

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  14. Immunotherapy in Advanced Prostate Cancer-Light at the End of the Tunnel?International journal of molecular sciences · 2022
    Review
  15. Review
  16. Role of glypican-1 in regulating multiple cellular signaling pathways.American journal of physiology. Cell physiology · 2021
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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

6 authors at 2 institutions in 1 country.

Maria E LundGlytherix Ltd, Suite 2 Ground Floor, 75 Talavera Road Macquarie Park, Sydney, NSW, 2113, Australia. maria.lund@glytherix.com.ORCID http://orcid.org/0000-0001-7360-5041
Christopher B HowardCentre for Advanced Imaging, The University of Queensland, St Lucia, QLD, 4072, Australia.
Kristofer J ThurechtCentre for Advanced Imaging, The University of Queensland, St Lucia, QLD, 4072, Australia.
Douglas H CampbellGlytherix Ltd, Suite 2 Ground Floor, 75 Talavera Road Macquarie Park, Sydney, NSW, 2113, Australia.
Stephen M MahlerAustralian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, QLD, 4072, Australia.
Bradley J WalshGlytherix Ltd, Suite 2 Ground Floor, 75 Talavera Road Macquarie Park, Sydney, NSW, 2113, Australia.
The University of Queensland · AUMacquarie University · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundGlypican-1 is a heparan sulfate proteoglycan that is overexpressed in prostate cancer (PCa), and a variety of solid tumors. Importantly, expression is restricted in normal tissue, making it an ideal tumor targeting antigen. Since there is clinical and preclinical evidence of the efficacy of Bispecific T cell Engager (BiTE) therapy in PCa, we sought to produce and test the efficacy of a GPC-1 targeted BiTE construct based on the Miltuximab

methodsThe single chain variable fragment (scFv) of Miltuximab

resultsBinding activity of MIL-38-CD3 to both cell surface-expressed and immobilised recombinant GPC-1 and CD3 was retained. MIL-38-CD3 was able to mediate the activation of peripheral blood T cells from healthy individuals, resulting in the release of inflammatory cytokines TNF and IFN-g. Activation was reliant on GPC-1 expression as MIL-38-CD3 mediated only low level T cell activation in the presence of C3 cells (constitutively low GPC-1 expression). Activated T cells were redirected to lyse PCa cell lines PC3 and DU-145 (GPC-1 moderate or high expression, respectively) but could not kill GPC-1 negative Raji cells. The expression of PD-1 was up-regulated on the surface of MIL-38-CD3 activated T cells, suggesting potential for synergy with checkpoint inhibition.

conclusionsThis study reports preclinical findings into the efficacy of targeting GPC-1 in PCa with BiTE construct MIL-38-CD3. We show the specificity and efficacy of the construct, supporting its further preclinical development.

Indexed as

T-Cell Antigen Receptor SpecificityAdenocarcinomaAntibodies, BispecificAntigens, CDAntigens, Differentiation, T-LymphocyteCD3 ComplexCD69 AntigensCell Line, TumorCoculture TechniquesCytokinesCytotoxicity, ImmunologicGlypicansHumansImmune Checkpoint InhibitorsInterleukin-2 Receptor alpha SubunitLectins, C-TypeAntibodies, BispecificAntigens, CDAntigens, Differentiation, T-LymphocyteCD3 ComplexCD69 AntigensCytokinesGlypicansGPC1 protein, humanIL2RA protein, humanImmune Checkpoint InhibitorsInterleukin-2 Receptor alpha SubunitLectins, C-TypeNeoplasm ProteinsRecombinant ProteinsSingle-Chain AntibodiesBiTECheckpoint inhibitorGlypican-1ImmunotherapyMiltuximab®Prostate cancer

Identifiers

PMID33302918
PMCPMC7727117
OpenAlexW3111257558

What OpenQuestion holds

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LicenceCC BY
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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.