Evidence map›Paper›PMID 31515721›Full record

ArticleAnnals of surgical oncology2019

Development of a Novel Humanized Monoclonal Antibody to Secreted Frizzled-Related Protein-2 That Inhibits Triple-Negative Breast Cancer and Angiosarcoma Growth In Vivo.

Denise Garcia, Patrick Nasarre, Ingrid V Bonilla, Eleanor Hilliard, Yuri K Peterson, Laura Spruill, Anne-Marie Broome, Elizabeth G Hill, Jason T Yustein, Shikhar Mehrotra and 1 more

Open access · greenAbstract read
In one paragraph

Article in Annals of surgical oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
0.6field-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

12 citing papers in PubMed, 11 citations in OpenAlex.

  1. Review
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  9. Review
  10. Article
  11. Multiple Roles of sFRP2 in Cardiac Development and Cardiovascular Disease.International journal of biological sciences · 2020
    Review
  12. Article
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

11 authors at 2 institutions in 1 country.

Denise GarciaDepartment of Surgery, Medical University of South Carolina, Charleston, SC, USA.
Patrick NasarreDepartment of Surgery, Medical University of South Carolina, Charleston, SC, USA.
Ingrid V BonillaDepartment of Surgery, Medical University of South Carolina, Charleston, SC, USA.
Eleanor HilliardDepartment of Surgery, Medical University of South Carolina, Charleston, SC, USA.
Yuri K PetersonDepartment of Drug Discovery and Biomedical Sciences, College of Pharmacy, Medical University of South Carolina, Charleston, SC, USA.
Laura SpruillDepartment of Pathology, Medical University of South Carolina, Charleston, SC, USA.
Anne-Marie BroomeDepartment of Cell and Molecular Pharmacology, Medical University of South Carolina, Charleston, SC, USA.
Elizabeth G HillDepartment of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USA.
Jason T YusteinDepartment of Pediatrics, Texas Children's Cancer and Hematology Centers, Baylor College of Medicine, Houston, TX, USA.
Shikhar MehrotraDepartment of Surgery, Medical University of South Carolina, Charleston, SC, USA.
Nancy Klauber-DeMoreDepartment of Surgery, Medical University of South Carolina, Charleston, SC, USA. demore@musc.edu.
Medical University of South Carolina · USBaylor College of Medicine · US

Funding

Translational Science Laboratory Shared ResourceP30CA138313 · NCI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI RAYMOND N. DUBOIS · 2009 to 2026
$42.7M
TRAINING PROGRAM FOR MEDICAL SCIENTISTST32GM008716 · NIGMS · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI DEMORE, NANCY · 1999 to 2024
$9.3M
Integrative Training in Oncogenic SignalingT32CA193201 · NCI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI HOWE, PHILIP H, LONG, DAVID THOMAS · 2016 to 2025
$3.7M
Oxidative stress and AICD in memory T cell persistenceR01CA138930 · NCI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI MEHROTRA, SHIKHAR · 2010 to 2014
$1.5M
Isolation and Characterization of Prostrate Antigen Specific High Affinity TCRR21CA137725 · NCI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI MEHROTRA, SHIKHAR · 2009 to 2010
$357k
NCI NIH HHS P30 CA138313NCI NIH HHS R01 CA138930NCI NIH HHS R21 CA137725NCI NIH HHS T32 CA193201NIGMS NIH HHS T32 GM008716NIH Clinical Center CA193201Sarcoma Foundation of America R01CA138930Sarcoma Foundation of America R21CA137725U.S. Department of Defense W81XWH-18-1-0007
6 · The paper itself

Abstract

backgroundWe previously reported that secreted frizzled-related protein-2 (SFRP2) is expressed in a variety of tumors, including sarcoma and breast carcinoma, and stimulates angiogenesis and inhibits tumor apoptosis. Therefore, we hypothesized that a humanized SFRP2 monoclonal antibody (hSFRP2 mAb) would inhibit tumor growth.

methodsThe lead hSFRP2 antibody was tested against a cohort of 22 healthy donors using a time course T-cell assay to determine the relative risk of immunogenicity. To determine hSFRP2 mAb efficacy, nude mice were subcutaneously injected with SVR angiosarcoma cells and treated with hSFRP2 mAb 4 mg/kg intravenously every 3 days for 3 weeks. We then injected Hs578T triple-negative breast cells into the mammary fat pad of nude mice and treated for 40 days. Control mice received an immunoglobulin (Ig) G1 control. The SVR and Hs578T tumors were then stained using a TUNEL assay to detect apoptosis.

resultsImmunogenicity testing of hSFRP2 mAb did not induce proliferative responses using a simulation index (SI) ≥ 2.0 (p < 0.05) threshold in any of the healthy donors. SVR angiosarcoma tumor growth was inhibited in vivo, evidenced by significant tumor volume reduction in the hSFRP2 mAb-treated group, compared with controls (n = 10, p < 0.001). Likewise, Hs578T triple-negative breast tumors were smaller in the hSFRP2 mAb-treated group compared with controls (n = 10, p < 0.001). The hSFRP2 mAb treatment correlated with an increase in tumor cell apoptosis (n = 11, p < 0.05). Importantly, hSFRP2 mAb treatment was not associated with any weight loss or lethargy.

conclusionWe present a novel hSFRP2 mAb with therapeutic potential in breast cancer and sarcoma that has no effect on immunogenicity.

Indexed as

ApoptosisAnimalsAntibodies, Monoclonal, HumanizedCell ProliferationFemaleHemangiosarcomaHumansMembrane ProteinsMiceMice, NudeNeovascularization, PathologicSecreted Frizzled-Related ProteinsTriple Negative Breast NeoplasmsTumor Cells, CulturedXenograft Model Antitumor AssaysAntibodies, Monoclonal, HumanizedMembrane ProteinsSecreted Frizzled-Related ProteinsSFRP2 protein, human

Identifiers

PMID31515721
PMCPMC8261905
OpenAlexW2972945316

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.