Evidence map›Paper›PMID 38225646›Full record

ArticleJournal of ovarian research2024

Virus-like particle vaccine displaying an external, membrane adjacent MUC16 epitope elicits ovarian cancer-reactive antibodies.

Hsin-Fang Tu, Margaret Wong, Ssu-Hsueh Tseng, Nattha Ingavat, Pola Olczak, Kin Israel Notarte, Chien-Fu Hung, Richard B S Roden

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of ovarian research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.7field-weighted citation impact, top 32% 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

3 citing papers in PubMed, 3 citations in OpenAlex.

  1. Article
  2. Review
  3. 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

8 authors at 2 institutions in 2 countries.

Hsin-Fang TuDepartment of Pathology, Johns Hopkins University, Baltimore, MD, 21287, USA.
Margaret WongDepartment of Pathology, Johns Hopkins University, Baltimore, MD, 21287, USA.
Ssu-Hsueh TsengDepartment of Pathology, Johns Hopkins University, Baltimore, MD, 21287, USA.
Nattha IngavatDownstream Processing (DSP), Bioprocessing Technology Institute (BTI), Agency for Science, Technology, and Research (A*STAR), Singapore, 138632, Singapore.
Pola OlczakDepartment of Pathology, Johns Hopkins University, Baltimore, MD, 21287, USA.
Kin Israel NotarteDepartment of Pathology, Johns Hopkins University, Baltimore, MD, 21287, USA.
Chien-Fu HungDepartment of Pathology, Johns Hopkins University, Baltimore, MD, 21287, USA.
Richard B S RodenDepartment of Pathology, Johns Hopkins University, Baltimore, MD, 21287, USA. roden@jhmi.edu.
Johns Hopkins University · USAgency for Science, Technology and Research · SG

Funding

Treatment of HIV- and HIV+ Patients with HPV16+ CIN2/3 Using pNGLV4a-hCRTE6E7L2 DNA vaccine administered intramuscularly via electroporationP50CA098252 · NCI · JOHNS HOPKINS UNIVERSITY · PI WARNER KING HUH, TZYY-CHOOU WU · 2003 to 2026
$53.5M
SPORE in Ovarian CancerP50CA228991 · NCI · JOHNS HOPKINS UNIVERSITY · PI Amanda Nickles Fader · 2018 to 2026
$20.5M
NCI NIH HHS P50 CA098252NCI NIH HHS P50 CA228991
6 · The paper itself

Abstract

backgroundMUC16 is a heavily glycosylated cell surface mucin cleaved in the tumor microenvironment to shed CA125. CA125 is a serum biomarker expressed by > 95% of non-mucinous advanced stage epithelial ovarian cancers. MUC16/CA125 contributes to the evasion of anti-tumor immunity, peritoneal spread and promotes carcinogenesis; consequently, it has been targeted with antibody-based passive and active immunotherapy. However, vaccination against this self-antigen likely requires breaking B cell tolerance and may trigger autoimmune disease. Display of self-antigens on virus-like particles (VLPs), including those produced with human papillomavirus (HPV) L1, can efficiently break B cell tolerance.

resultsA 20 aa juxta-membrane peptide of the murine MUC16 (mMUC16) or human MUC16 (hMUC16) ectodomain was displayed either via genetic insertion into an immunodominant loop of HPV16 L1-VLPs between residues 136/137, or by chemical coupling using malemide to cysteine sulfhydryl groups on their surface. Female mice were vaccinated intramuscularly three times with either DNA expressing L1-MUC16 fusions via electroporation, or with alum-formulated VLP chemically-coupled to MUC16 peptides. Both regimens were well tolerated, and elicited MUC16-specific serum IgG, although titers were higher in mice vaccinated with MUC16-coupled VLP on alum as compared to L1-MUC16 DNA vaccination. Antibody responses to mMUC16-targeted vaccination cross-reacted with hMUC16 peptide, and vice versa; both were reactive with the surface of CA125+ OVCAR3 cells, but not SKOV3 that lack detectable CA125 expression. Interestingly, vaccination of mice with mMUC16 peptide mixed with VLP and alum elicited mMUC16-specific IgG, implying VLPs provide robust T help and that coupling may not be required to break tolerance to this epitope.

conclusionVaccination with VLP displaying the 20 aa juxta-membrane MUC16 ectodomain, which includes the membrane proximal cleavage site, is likely to be well tolerated and induce IgG targeting ovarian cancer cells, even after CA125 is shed.

Indexed as

Alum CompoundsOvarian NeoplasmsVaccines, Virus-Like ParticleAnimalsApoptosisCA-125 AntigenCell Line, TumorDNAEpitopesFemaleHumansImmunoglobulin GMembrane ProteinsMicePeptidesTumor MicroenvironmentAlum Compoundsaluminum sulfateCA-125 AntigenDNAEpitopesImmunoglobulin GMembrane ProteinsMUC16 protein, humanPeptidesVaccines, Virus-Like ParticleAntibodyCA125MUC16Ovarian cancerVaccinationVirus-like particle

Identifiers

PMID38225646
PMCPMC10790439
OpenAlexW4390919313

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.