Evidence map›Paper›PMID 31289278›Full record

ArticleScientific reports2019

Antitumor effects of the GM3(Neu5Gc) ganglioside-specific humanized antibody 14F7hT against Cmah-transfected cancer cells.

Denise Dorvignit, Kayluz F Boligan, Ernesto Relova-Hernández, Marilyn Clavell, Armando López, Mayrel Labrada, Hans-Uwe Simon, Alejandro López-Requena, Circe Mesa, Stephan von Gunten

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

19 citing papers in PubMed, 30 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

10 authors at 3 institutions in 3 countries.

Denise DorvignitImmunobiology Division, Center of Molecular Immunology, Havana, 11600, Cuba.ORCID https://orcid.org/0000-0003-2844-4108
Kayluz F BoliganInstitute of Pharmacology, University of Bern, Bern, 3010, Switzerland.
Ernesto Relova-HernándezImmunobiology Division, Center of Molecular Immunology, Havana, 11600, Cuba.
Marilyn ClavellImmunobiology Division, Center of Molecular Immunology, Havana, 11600, Cuba.
Armando LópezAnimal House Department, Center of Molecular Immunology, Havana, 11600, Cuba.
Mayrel LabradaImmunobiology Division, Center of Molecular Immunology, Havana, 11600, Cuba.
Hans-Uwe SimonInstitute of Pharmacology, University of Bern, Bern, 3010, Switzerland.
Alejandro López-RequenaImmunobiology Division, Center of Molecular Immunology, Havana, 11600, Cuba.ORCID http://orcid.org/0000-0002-6951-8321
Circe MesaImmunobiology Division, Center of Molecular Immunology, Havana, 11600, Cuba. circe@cim.sld.cu.
Stephan von GuntenInstitute of Pharmacology, University of Bern, Bern, 3010, Switzerland.
Center of Molecular Immunology (Cuba) · CUUniversity of Bern · CHAblynx (Belgium) · BE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The GM3(Neu5Gc) ganglioside represents a tumor-specific antigen that is considered a promising target for cancer immunotherapy. We previously demonstrated that the humanized antibody 14F7hT, specific for this ganglioside, exhibited significant antitumor effects in preclinical hematological tumor models. As this antibody recognizes human tumor tissues from several origins, we addressed its potential effect on different tumor types. The use of cell lines for testing GM3(Neu5Gc)-targeting strategies, in particular for human malignancies, is complicated by the absence in humans of functional cytidine monophospho-N-acetyl-neuraminic acid hydroxylase (CMAH), the enzyme required for Neu5Gc sialic acid biosynthesis. Quantitative flow cytometry revealed the absence of surface GM3(Neu5Gc) in several human but also mouse cell lines, in the last case due to low expression of the enzyme. Hypoxia-induced expression of this ganglioside on human SKOV3 cells was observed upon culture in Neu5Gc-containing medium without evidence for CMAH-independent biosynthesis. However, only transfection of the mouse Cmah gene into human SKOV3 and mouse 3LL cells induced a stable expression of GM3(Neu5Gc) on the cancer cell surface, resulting in effective models to evaluate the antitumor responses by 14F7hT in vitro and in vivo. This antibody exerted antibody-dependent cell-mediated cytotoxicity (ADCC) and in vivo antitumor effects on these Cmah-transfected non-hematological tumors from both mouse and human origin. These results contribute to validate GM3(Neu5Gc) as a relevant target for cancer immunotherapy and reinforces the value of 14F7hT as a novel anti-cancer drug.

Indexed as

AnimalsAntibodies, Monoclonal, HumanizedAntibody-Dependent Cell CytotoxicityAntigens, NeoplasmAntineoplastic AgentsFemaleG(M3) GangliosideMiceMice, Inbred BALB CMice, Inbred C57BLMixed Function OxygenasesNeoplasmsTumor Cells, CulturedAntibodies, Monoclonal, HumanizedAntigens, NeoplasmAntineoplastic AgentsCMPacetylneuraminate monooxygenaseG(M3) GangliosideMixed Function Oxygenases

Identifiers

PMID31289278
PMCPMC6616363
OpenAlexW2956637914

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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.