Evidence map›Paper›PMID 32943549›Full record

ArticleMolecular cancer therapeutics2020

Microparticle Encapsulation of a Prostate-targeted Biologic for the Treatment of Liver Metastases in a Preclinical Model of Castration-resistant Prostate Cancer.

Oliver C Rogers, Lizamma Antony, Oren Levy, Nitin Joshi, Brian W Simons, Susan L Dalrymple, D Marc Rosen, Andrew Pickering, Haoyue Lan, Heidi Kuang and 7 more

Open access · greenAbstract read
In one paragraph

Article in Molecular cancer therapeutics, 2020. 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
0.3field-weighted citation impact, top 39% 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, 3 citations in OpenAlex.

  1. Drug and Clinical Candidate Drug Data in ChEMBL.Journal of medicinal chemistry · 2025
    Review
  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

17 authors at 5 institutions in 3 countries.

Oliver C RogersDepartment of Pharmacology and Molecular Sciences, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Lizamma AntonyDepartment of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland.
Oren LevyCenter for Nanomedicine and Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
Nitin JoshiCenter for Nanomedicine and Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
Brian W SimonsDepartment of Molecular and Comparative Pathobiology, Johns Hopkins University, Baltimore, Maryland.
Susan L DalrympleDepartment of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland.
D Marc RosenDepartment of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland.
Andrew PickeringHarvard - MIT Division of Health Sciences and Technology, Cambridge, Massachusetts.ORCID 0000-0002-1496-7752
Haoyue LanHarvard - MIT Division of Health Sciences and Technology, Cambridge, Massachusetts.
Heidi KuangHarvard - MIT Division of Health Sciences and Technology, Cambridge, Massachusetts.ORCID 0000-0001-9379-6228
Sudhir H RanganathHarvard - MIT Division of Health Sciences and Technology, Cambridge, Massachusetts.ORCID 0000-0003-0732-0341
Lei ZhengDepartment of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland.
Jeffrey M KarpCenter for Nanomedicine and Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.ORCID 0000-0002-4752-7374
S Peter HowardDepartment of Microbiology and Immunology, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.ORCID 0000-0001-7961-7000
Samuel R DenmeadeDepartment of Pharmacology and Molecular Sciences, Johns Hopkins Medical Institutions, Baltimore, Maryland.
John T IsaacsDepartment of Pharmacology and Molecular Sciences, Johns Hopkins Medical Institutions, Baltimore, Maryland.ORCID 0000-0002-3854-4658
W Nathaniel BrennenDepartment of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland. wbrenne2@jhmi.edu.ORCID 0000-0001-9807-7433
Johns Hopkins University · USHarvard–MIT Division of Health Sciences and Technology · USSidney Kimmel Comprehensive Cancer Center · USBrigham and Women's Hospital · USUniversity of Saskatchewan · CA

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI WILLIAM George NELSON · 1985 to 2026
$208.6M
TRANSGENIC MODELS FOR PROSTATE CANCER AND AUTOIMMUNITYP50CA058236 · NCI · JOHNS HOPKINS UNIVERSITY · PI DENMEADE, SAMUEL R · 1992 to 2020
$43.9M
Engineered Induction of a Stem Cell Homing ResponseR01HL095722 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI KARP, JEFFREY MICHAEL · 2010 to 2018
$3.9M
NCI NIH HHS P30 CA006973NCI NIH HHS P50 CA058236NHLBI NIH HHS R01 HL095722
6 · The paper itself

Abstract

PRX302 is a highly potent, mutant bacterial pore-forming biologic protoxin engineered for selective activation by PSA, a serine protease expressed by benign and malignant prostate epithelial cells. Although being developed as a local therapy for benign prostatic hyperplasia and localized prostate cancer, PRX302 cannot be administered systemically as a treatment for metastatic disease due to binding to ubiquitously expressed glycosylphosphatidylinositol (GPI)-anchored proteins, which leads to poor accumulation within the tumor microenvironment. To overcome this limitation, poly-lactic-co-glycolic acid (PLGA) microparticles encapsulating the protoxin were developed, which are known to accumulate in the liver, a major site of metastasis for prostate cancer and other solid tumors. A highly sensitive and reproducible sandwich ELISA to quantify PRX302 released from microparticles was developed. Utilizing this assay, PRX302 release from different microparticle formulations was assessed over multiple days. Hemolysis assays documented PSA-dependent pore formation and lytic potential (i.e., function) of the released protoxin. MTT assays demonstrated that conditioned supernatant from PRX302-loaded, but not blank (i.e., unloaded), PLGA microparticles was highly cytotoxic to PC3 and DU145 human prostate cancer cells in the presence of exogenous PSA. Microparticle encapsulation prevented PRX302 from immediately interacting with GPI-anchored proteins as demonstrated in a competition assay, which resulted in an increased therapeutic index and significant antitumor efficacy following a single dose of PRX302-loaded microparticles in a preclinical model of prostate cancer liver metastasis with no obvious toxicity. These results document that PRX302 released from PLGA microparticles demonstrate

Indexed as

Drug CompoundingAnimalsAntineoplastic AgentsBacterial ToxinsBiological ProductsCell Line, TumorDisease Models, AnimalHemolysisHumansLiver NeoplasmsMalePolylactic Acid-Polyglycolic Acid CopolymerPore Forming Cytotoxic ProteinsProstatic Neoplasms, Castration-ResistantProtein BindingXenograft Model Antitumor AssaysAntineoplastic AgentsBacterial ToxinsBiological ProductsPolylactic Acid-Polyglycolic Acid CopolymerPore Forming Cytotoxic ProteinsPRX302

Identifiers

PMID32943549
PMCPMC8130453
OpenAlexW3087748453

What OpenQuestion holds

Textmetadata
LicenceTDM
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.