Evidence map›Paper›PMID 23918357›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2013

Proteasome activator complex PA28 identified as an accessible target in prostate cancer by in vivo selection of human antibodies.

David Sánchez-Martín, Jorge Martínez-Torrecuadrada, Tambet Teesalu, Kazuki N Sugahara, Ana Alvarez-Cienfuegos, Pilar Ximénez-Embún, Rodrigo Fernández-Periáñez, M Teresa Martín, Irene Molina-Privado, Isabel Ruppen-Cañás and 11 more

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.5field-weighted citation impact, top 17% 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

22 citing papers in PubMed, 39 citations in OpenAlex.

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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 5 institutions in 3 countries.

David Sánchez-MartínMolecular Immunology Unit, Hospital Universitario Puerta de Hierro Majadahonda, 28222 Majadahonda, Madrid, Spain.
Jorge Martínez-Torrecuadrada
Tambet Teesalu
Kazuki N Sugahara
Ana Alvarez-Cienfuegos
Pilar Ximénez-Embún
Rodrigo Fernández-Periáñez
M Teresa Martín
Irene Molina-Privado
Isabel Ruppen-Cañás
Ana Blanco-Toribio
Marta Cañamero
Angel M Cuesta
Marta Compte
Leonor Kremer
Carmen Bellas
Vanesa Alonso-Camino
Irene Guijarro-Muñoz
Laura Sanz
Erkki Ruoslahti
Luis Alvarez-Vallina
Hospital Universitario Puerta de Hierro Majadahonda · ESSpanish National Cancer Research Centre · ESConsejo Superior de Investigaciones Científicas · ESSanford Burnham Prebys Medical Discovery Institute · USUniversity of California, Santa Barbara · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Antibody cancer therapies rely on systemically accessible targets and suitable antibodies that exert a functional activity or deliver a payload to the tumor site. Here, we present proof-of-principle of in vivo selection of human antibodies in tumor-bearing mice that identified a tumor-specific antibody able to deliver a payload and unveils the target antigen. By using an ex vivo enrichment process against freshly disaggregated tumors to purge the repertoire, in combination with in vivo biopanning at optimized phage circulation time, we have identified a human domain antibody capable of mediating selective localization of phage to human prostate cancer xenografts. Affinity chromatography followed by mass spectrometry analysis showed that the antibody recognizes the proteasome activator complex PA28. The specificity of soluble antibody was confirmed by demonstrating its binding to the active human PA28αβ complex. Whereas systemically administered control phage was confined in the lumen of blood vessels of both normal tissues and tumors, the selected phage spread from tumor vessels into the perivascular tumor parenchyma. In these areas, the selected phage partially colocalized with PA28 complex. Furthermore, we found that the expression of the α subunit of PA28 [proteasome activator complex subunit 1 (PSME1)] is elevated in primary and metastatic human prostate cancer and used anti-PSME1 antibodies to show that PSME1 is an accessible marker in mouse xenograft tumors. These results support the use of PA28 as a tumor marker and a potential target for therapeutic intervention in prostate cancer.

Indexed as

AnimalsAntibodies, NeoplasmAntibody SpecificityBiomarkers, TumorBlotting, WesternCell Surface Display TechniquesChromatography, AffinityChromatography, LiquidDrug Delivery SystemsEnzyme-Linked Immunosorbent AssayFluorescent Antibody TechniqueHumansImmunohistochemistryImmunoprecipitationImmunotherapyMaleAntibodies, NeoplasmBiomarkers, TumorMuscle ProteinsProteasome Endopeptidase ComplexPSME1 protein, humanphage displayphage libraryphysiological selectionsingle domain antibodytumor-associated antigen

Identifiers

PMID23918357
PMCPMC3752212
OpenAlexW2168017406

What OpenQuestion holds

Textmetadata
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.