Evidence map›Paper›PMID 31653037›Full record

ArticleMolecules (Basel, Switzerland)2019

Multimerization through Pegylation Improves Pharmacokinetic Properties of scFv Fragments of GD2-Specific Antibodies.

Irina V Kholodenko, Daniel V Kalinovsky, Elena V Svirshchevskaya, Igor I Doronin, Maria V Konovalova, Alexey V Kibardin, Tatyana V Shamanskaya, Sergey S Larin, Sergey M Deyev, Roman V Kholodenko

Open access · goldAbstract read
In one paragraph

Article in Molecules (Basel, Switzerland), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.0field-weighted citation impact, top 13% 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

16 citing papers in PubMed, 29 citations in OpenAlex.

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  13. Gangliosides and Neuroblastomas.International journal of molecular sciences · 2020
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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 4 institutions in 1 country.

Irina V KholodenkoOrekhovich Institute of Biomedical Chemistry, 10, Pogodinskaya St., Moscow 119121, Russia. irkhol@yandex.ru.ORCID 0000-0002-4079-5210
Daniel V KalinovskyShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10, Miklukho-Maklaya St., Moscow 117997, Russia. dcalinovschi@yahoo.com.ORCID 0000-0001-8773-2797
Elena V SvirshchevskayaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10, Miklukho-Maklaya St., Moscow 117997, Russia. esvir@mx.ibch.ru.
Igor I DoroninShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10, Miklukho-Maklaya St., Moscow 117997, Russia. doroninii@gmail.com.
Maria V KonovalovaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10, Miklukho-Maklaya St., Moscow 117997, Russia. mariya.v.konovalova@gmail.com.
Alexey V KibardinD. Rogachev Federal Research Center of Pediatric Hematology, Oncology and Immunology, 1, Samory Mashela St., Moscow 117997, Russia. alexey.kibardin@gmail.com.
Tatyana V ShamanskayaD. Rogachev Federal Research Center of Pediatric Hematology, Oncology and Immunology, 1, Samory Mashela St., Moscow 117997, Russia. shamanskaya.tatyana@gmail.com.
Sergey S LarinD. Rogachev Federal Research Center of Pediatric Hematology, Oncology and Immunology, 1, Samory Mashela St., Moscow 117997, Russia. sergei_larin@mail.ru.ORCID 0000-0002-2128-0078
Sergey M DeyevShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10, Miklukho-Maklaya St., Moscow 117997, Russia. deyev@mail.ibch.ru.
Roman V KholodenkoShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10, Miklukho-Maklaya St., Moscow 117997, Russia. khol@mail.ru.ORCID 0000-0001-6083-6588
Institute of Bioorganic Chemistry · RUDmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology · RUInstitute of Biomedical Chemistry · RUSechenov University · RU

Funding

Russian Science Foundation 18-15-00360
6 · The paper itself

Abstract

Antigen-binding fragments of antibodies specific to the tumor-associated ganglioside GD2 are well poised to play a substantial role in modern GD2-targeted cancer therapies, however, rapid elimination from the body and reduced affinity compared to full-length antibodies limit their therapeutic potential. In this study, scFv fragments of GD2-specific antibodies 14.18 were produced in a mammalian expression system that specifically bind to ganglioside GD2, followed by site-directed pegylation to generate mono-, di-, and tetra-scFv fragments. Fractionated pegylated dimers and tetramers of scFv fragments showed significant increase of the binding to GD2 which was not accompanied by cross-reactivity with other gangliosides. Pegylated multimeric di-scFvs and tetra-scFvs exhibited cytotoxic effects in GD2-positive tumor cells, while their circulation time in blood significantly increased compared with monomeric antibody fragments. We also demonstrated a more efficient tumor uptake of the multimers in a syngeneic GD2-positive mouse cancer model. The findings of this study provide the rationale for improving therapeutic characteristics of GD2-specific antibody fragments by multimerization and propose a strategy to generate such molecules. On the basis of multimeric antibody fragments, bispecific antibodies and conjugates with cytotoxic drugs or radioactive isotopes may be developed that will possess improved pharmacokinetic and pharmacodynamic properties.

Indexed as

Antineoplastic Agents, ImmunologicalNeoplasms, ExperimentalSingle-Chain AntibodiesAnimalsCell Line, TumorGangliosidesHumansMiceMice, Inbred BALB CPolyethylene GlycolsAntineoplastic Agents, Immunologicalganglioside, GD2GangliosidesPolyethylene GlycolsSingle-Chain Antibodiesantibody fragmentscancerganglioside GD2immunotherapymultimerizationneuroblastomapegylation

Identifiers

PMID31653037
PMCPMC6864547
OpenAlexW2981320757

What OpenQuestion holds

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LicenceCC BY
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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.