Evidence map›Paper›PMID 39113562›Full record

ArticlemAbs

Discovery of a novel highly specific, fully human PSCA antibody and its application as an antibody-drug conjugate in prostate cancer.

Xiaojie Chu, Seungmin Shin, Du-San Baek, Liyong Zhang, Alex Conard, Megan Shi, Ye-Jin Kim, Cynthia Adams, Maggie Hines, Xianglei Liu and 6 more

Abstract read
In one paragraph

Article in mAbs. 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
–field-weighted citation impact
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.

  1. Article
  2. 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

16 authors.

Xiaojie ChuCenter for Antibody Therapeutics, Division of Infectious Diseases, Department of Medicine, University of Pittsburgh Medical School, Pittsburgh, PA, USA.
Seungmin ShinCenter for Antibody Therapeutics, Division of Infectious Diseases, Department of Medicine, University of Pittsburgh Medical School, Pittsburgh, PA, USA.
Du-San BaekGLPG, Pittsburgh, PA, USA.
Liyong ZhangHillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA.
Alex ConardGLPG, Pittsburgh, PA, USA.
Megan ShiComputational and System Biology, School of Medicine, University of Pittsburgh, Pittsburgh, USA.
Ye-Jin KimGLPG, Pittsburgh, PA, USA.
Cynthia AdamsGLPG, Pittsburgh, PA, USA.
Maggie HinesCenter for Antibody Therapeutics, Division of Infectious Diseases, Department of Medicine, University of Pittsburgh Medical School, Pittsburgh, PA, USA.
Xianglei LiuCenter for Antibody Therapeutics, Division of Infectious Diseases, Department of Medicine, University of Pittsburgh Medical School, Pittsburgh, PA, USA.
Chuan ChenCenter for Antibody Therapeutics, Division of Infectious Diseases, Department of Medicine, University of Pittsburgh Medical School, Pittsburgh, PA, USA.
Zehua SunGLPG, Pittsburgh, PA, USA.
Dontcho V JelevCenter for Antibody Therapeutics, Division of Infectious Diseases, Department of Medicine, University of Pittsburgh Medical School, Pittsburgh, PA, USA.
John W MellorsCenter for Antibody Therapeutics, Division of Infectious Diseases, Department of Medicine, University of Pittsburgh Medical School, Pittsburgh, PA, USA.
Dimiter S DimitrovCenter for Antibody Therapeutics, Division of Infectious Diseases, Department of Medicine, University of Pittsburgh Medical School, Pittsburgh, PA, USA.
Wei LiCenter for Antibody Therapeutics, Division of Infectious Diseases, Department of Medicine, University of Pittsburgh Medical School, Pittsburgh, PA, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Prostate stem cell antigen (PSCA) is expressed in all stages of prostate cancer, including in advanced androgen-independent tumors and bone metastasis. PSCA may associate with prostate carcinogenesis and lineage plasticity in prostate cancer. PSCA is also a promising theranostic marker for a variety of other solid tumors, including pancreatic adenocarcinoma and renal cell carcinoma. Here, we identified a novel fully human PSCA antibody using phage display methodology. The structure-based affinity maturation yielded a high-affinity binder, F12, which is highly specific and does not bind to 6,000 human membrane proteins based on a membrane proteome array assay. F12 targets PSCA amino acids 63-69 as tested by the peptide scanning microarray, and it cross-reacts with the murine PSCA. IgG1 F12 efficiently internalizes into PSCA-expressing tumor cells. The antimitotic reagent monomethyl auristatin E (MMAE)-conjugated IgG1 F12 (ADC, F12-MMAE) exhibits dose-dependent efficacy and specificity in a human prostate cancer PC-3-PSCA xenograft NSG mouse model. This is a first reported ADC based on a fully human PSCA antibody and MMAE that is characterized in a xenograft murine model, which warrants further optimizations and investigations in additional preclinical tumor models, including prostate and other solid tumors.

Indexed as

Antigens, NeoplasmGPI-Linked ProteinsImmunoconjugatesNeoplasm ProteinsProstatic NeoplasmsXenograft Model Antitumor AssaysAnimalsAntibodies, MonoclonalCell Line, TumorHumansImmunoglobulin GMaleMiceOligopeptidesAntibodies, MonoclonalAntigens, NeoplasmGPI-Linked ProteinsImmunoconjugatesImmunoglobulin Gmonomethyl auristatin ENeoplasm ProteinsOligopeptidesPSCA protein, humanAntibody drug conjugatefully human antibodymonomethyl auristatin Eprostate cancerPSCAtumor xenograft mouse model

Identifiers

PMID39113562
PMCPMC11312989

What OpenQuestion holds

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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.