Evidence map›Paper›PMID 26216943›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2015

AAV9 delivering a modified human Mullerian inhibiting substance as a gene therapy in patient-derived xenografts of ovarian cancer.

David Pépin, Amanda Sosulski, Lihua Zhang, Dan Wang, Vinod Vathipadiekal, Katherine Hendren, Caroline M Coletti, Aaron Yu, Cesar M Castro, Michael J Birrer and 2 more

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

Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
4.4field-weighted citation impact, top 5% 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

34 citing papers in PubMed, 54 citations in OpenAlex.

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  12. Single-cell sequencing reveals suppressive transcriptional programs regulated by MIS/AMH in neonatal ovaries.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
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  18. CAR T Cells Targeting MISIIR for the Treatment of Ovarian Cancer and Other Gynecologic Malignancies.Molecular therapy : the journal of the American Society of Gene Therapy · 2020
    Article
  19. Article
  20. 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

12 authors at 3 institutions in 1 country.

David PépinPediatric Surgical Research Laboratories, Massachusetts General Hospital, Department of Surgery, Harvard Medical School, Boston, MA 02114;
Amanda SosulskiPediatric Surgical Research Laboratories, Massachusetts General Hospital, Department of Surgery, Harvard Medical School, Boston, MA 02114;
Lihua ZhangPediatric Surgical Research Laboratories, Massachusetts General Hospital, Department of Surgery, Harvard Medical School, Boston, MA 02114;
Dan WangGene Therapy Center, University of Massachusetts Medical School, Worcester, MA 01655;
Vinod VathipadiekalGynecological Oncology, Massachusetts General Hospital, Department of Medicine, Harvard Medical School, Boston, MA 02114.
Katherine HendrenPediatric Surgical Research Laboratories, Massachusetts General Hospital, Department of Surgery, Harvard Medical School, Boston, MA 02114;
Caroline M ColettiPediatric Surgical Research Laboratories, Massachusetts General Hospital, Department of Surgery, Harvard Medical School, Boston, MA 02114;
Aaron YuPediatric Surgical Research Laboratories, Massachusetts General Hospital, Department of Surgery, Harvard Medical School, Boston, MA 02114;
Cesar M CastroGynecological Oncology, Massachusetts General Hospital, Department of Medicine, Harvard Medical School, Boston, MA 02114.
Michael J BirrerGynecological Oncology, Massachusetts General Hospital, Department of Medicine, Harvard Medical School, Boston, MA 02114.
Guangping GaoGene Therapy Center, University of Massachusetts Medical School, Worcester, MA 01655;
Patricia K DonahoePediatric Surgical Research Laboratories, Massachusetts General Hospital, Department of Surgery, Harvard Medical School, Boston, MA 02114; pdonahoe@partners.org.
Harvard University · USMassachusetts General Hospital · USUniversity of Massachusetts Chan Medical School · US

Funding

MULLERIAN INHIBITING SUBSTANCER01CA017393 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI DONAHOE, PATRICIA K · 1985 to 2009
$4.0M
NCI NIH HHS R01 CA017393NCI NIH HHS R01CA17393
6 · The paper itself

Abstract

To improve ovarian cancer patient survival, effective treatments addressing chemoresistant recurrences are particularly needed. Mullerian inhibiting substance (MIS) has been shown to inhibit the growth of a stem-like population of ovarian cancer cells. We have recently engineered peptide modifications to human MIS [albumin leader Q425R MIS (LRMIS)] that increase production and potency in vitro and in vivo. To test this novel therapeutic peptide, serous malignant ascites from highly resistant recurrent ovarian cancer patients were isolated and amplified to create low-passage primary cell lines. Purified recombinant LRMIS protein successfully inhibited the growth of cancer spheroids in vitro in a panel of primary cell lines in four of six patients tested. Adeno-associated virus (AAV) -delivered gene therapy has undergone a clinical resurgence with a good safety profile and sustained gene expression. Therefore, AAV9 was used as a single i.p. injection to deliver LRMIS to test its efficacy in inhibiting growth of palpable tumors in patient-derived ovarian cancer xenografts from ascites (PDXa). AAV9-LRMIS monotherapy resulted in elevated and sustained blood concentrations of MIS, which significantly inhibited the growth of three of five lethal chemoresistant serous adenocarcinoma PDXa models without signs of measurable or overt toxicity. Finally, we tested the frequency of MIS type II receptor expression in a tissue microarray of serous ovarian tumors by immunohistochemistry and found that 88% of patients bear tumors that express the receptor. Taken together, these preclinical data suggest that AAV9-LRMIS provides a potentially well-tolerated and effective treatment strategy poised for testing in patients with chemoresistant serous ovarian cancer.

Indexed as

Genetic TherapyXenograft Model Antitumor AssaysAdultAgedAged, 80 and overAnimalsAnti-Mullerian HormoneAscitesBiomarkers, TumorCarcinogenesisCell Line, TumorCell ProliferationDependovirusFemaleHumansMiceAnti-Mullerian Hormoneanti-Mullerian hormone receptorBiomarkers, TumorReceptors, PeptideReceptors, Transforming Growth Factor betaRecombinant Fusion ProteinsAAV9anti-Mullerian hormoneMISovarian cancerPDX

Identifiers

PMID26216943
PMCPMC4538667
OpenAlexW2157544609

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.