Pegylated Trastuzumab Fragments Acquire an Increased in Vivo Stability but Show a Largely Reduced Affinity for the Target Antigen (292 views visite) (PDF public pubblico 236 views visite)
Int J Mol Sc (ISSN: 1422-0067, 1661-6596, 1422-0067linking), 2016 Apr 1; 17(4): N/D-N/D.
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Paper type Tipo di articolo: Journal Article,
Impact factor: 3.226, 5-year impact factor Impact factor a 5 anni: 3.482
Url: https://www.scopus.com/inward/record.uri?eid=2-s2.0-84962385296&doi=10.3390%2fijms17040491&partnerID=40&md5=35ef6085d9521fc0431927bb55bd407e
Keywords Parole chiave: Fab, Pegylation, Antibody Fragment, Papain Digestion, Pepsin Digestion, Pharmacokinetics,
Affiliations Affiliazioni:
*** IBB - CNR ***
Bioker srl-Multimedica Group, c/o Institute of Genetics and
Biophysics, National Research Council (CNR-IGB) via P. Castellino 111,
Institute of Biostructure and Bioimaging, National Research Council (IBB-CNR), via Mezzocannone 16, 80134 Napoli, Italy
Centro Interuniversitario di Ricerca sui Peptidi Bioattivi
(CIRPeB), University of Naples Federico II, via Mezzocannone 16, 80134
Department of Clinical Medicine and Surgery, University of Naples Federico II, 80134 Napoli, Italy
Department of Biomedical, Biotechnological and Translational
Science (S.Bi.Bi.T.), Università di Parma, 43126 Parma, Italy
class="page" title="Page 1">
carlamarra78@yahoo.it (C.M.); silvia.scaramuzza@multimedica.it (S.S.); annalisa.politano@gmail.com (A.P.);
riccardo.sanna@multimedica.it (R.S.); giancarlo.tonon@multimedica.it (G.T.)
80134 Napoli, Italy; giuseppina.foca@gmail.com (G.F.); menotti.ruvo@unina.it (M.R.)
43126 Parma, Italy; gloria.saccani@unipr.it
Correspondence: fabio.selis@multimedica.it (F.S.); annamaria.sandomenico@gmail.com (A.S.);
Tel.: +39-081-613-2423 (F.S.); +39-081-253-6644 (A.S.)
These authors contributed equally to this work.
References Riferimenti:
Not available. Non disponibili.
Int J Mol Sc (ISSN: 1422-0067, 1661-6596, 1422-0067linking), 2016 Apr 1; 17(4): N/D-N/D.
Export to Esporta in BibTeX Export to Esporta in EndNote
Paper type Tipo di articolo: Journal Article,
Impact factor: 3.226, 5-year impact factor Impact factor a 5 anni: 3.482
Url: https://www.scopus.com/inward/record.uri?eid=2-s2.0-84962385296&doi=10.3390%2fijms17040491&partnerID=40&md5=35ef6085d9521fc0431927bb55bd407e
Keywords Parole chiave: Fab, Pegylation, Antibody Fragment, Papain Digestion, Pepsin Digestion, Pharmacokinetics,
Affiliations Affiliazioni:
*** IBB - CNR ***
Bioker srl-Multimedica Group, c/o Institute of Genetics and
Biophysics, National Research Council (CNR-IGB) via P. Castellino 111,
Institute of Biostructure and Bioimaging, National Research Council (IBB-CNR), via Mezzocannone 16, 80134 Napoli, Italy
Centro Interuniversitario di Ricerca sui Peptidi Bioattivi
(CIRPeB), University of Naples Federico II, via Mezzocannone 16, 80134
Department of Clinical Medicine and Surgery, University of Naples Federico II, 80134 Napoli, Italy
Department of Biomedical, Biotechnological and Translational
Science (S.Bi.Bi.T.), Università di Parma, 43126 Parma, Italy
class="page" title="Page 1">
carlamarra78@yahoo.it (C.M.); silvia.scaramuzza@multimedica.it (S.S.); annalisa.politano@gmail.com (A.P.);
riccardo.sanna@multimedica.it (R.S.); giancarlo.tonon@multimedica.it (G.T.)
80134 Napoli, Italy; giuseppina.foca@gmail.com (G.F.); menotti.ruvo@unina.it (M.R.)
43126 Parma, Italy; gloria.saccani@unipr.it
Correspondence: fabio.selis@multimedica.it (F.S.); annamaria.sandomenico@gmail.com (A.S.);
Tel.: +39-081-613-2423 (F.S.); +39-081-253-6644 (A.S.)
These authors contributed equally to this work.
References Riferimenti:
Not available. Non disponibili.
Pegylated Trastuzumab Fragments Acquire an Increased in Vivo Stability but Show a Largely Reduced Affinity for the Target Antigen
Last modified by Ultima modifica di Marco Comerci on in data Sunday 12 July 2020, 13:14:47
292 views visite. Last view on Ultima visita in data Wednesday 16 June 2021, 14:25:58
PEGylation of biomolecules is a major approach to increase blood stream half-life, stability
and solubility of biotherapeutics and to reduce their immunogenicity, aggregation potential and
unspecific interactions with other proteins and tissues. Antibodies have generally long half-lives
due to high molecular mass and stability toward proteases, however their size lowers to some extent
their potential because of a reduced ability to penetrate tissues, especially those of tumor origin.
Fab or otherwise engineered smaller fragments are an alternative but are less stable and are much
less well retained in circulation. We have here investigated the effects of various PEGylations on
the binding properties and in vivo half-life of Fab fragments derived from the enzymatic splitting of
Trastuzumab. We find that PEGylation increases the half-life of the molecules but also strongly affects
the ability to recognize the target antigen in a way that is dependent on the extent and position of the
chemical modification. Data thus support the concept that polyethylene glycol (PEG) conjugation on
Trastuzumab Fabs increases half-life but reduces their affinity and this is a fine balance, which must
be carefully considered for the design of strategies based on the use of antibody fragments.
and solubility of biotherapeutics and to reduce their immunogenicity, aggregation potential and
unspecific interactions with other proteins and tissues. Antibodies have generally long half-lives
due to high molecular mass and stability toward proteases, however their size lowers to some extent
their potential because of a reduced ability to penetrate tissues, especially those of tumor origin.
Fab or otherwise engineered smaller fragments are an alternative but are less stable and are much
less well retained in circulation. We have here investigated the effects of various PEGylations on
the binding properties and in vivo half-life of Fab fragments derived from the enzymatic splitting of
Trastuzumab. We find that PEGylation increases the half-life of the molecules but also strongly affects
the ability to recognize the target antigen in a way that is dependent on the extent and position of the
chemical modification. Data thus support the concept that polyethylene glycol (PEG) conjugation on
Trastuzumab Fabs increases half-life but reduces their affinity and this is a fine balance, which must
be carefully considered for the design of strategies based on the use of antibody fragments.
Pegylated Trastuzumab Fragments Acquire an Increased in Vivo Stability but Show a Largely Reduced Affinity for the Target Antigen
Pegylated Trastuzumab Fragments Acquire an Increased in Vivo Stability but Show a Largely Reduced Affinity for the Target Antigen
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Sandomenico A, Sivaccumar JP, Ruvo M
* Evolution of Escherichia coli Expression System in Producing Antibody Recombinant Fragments (45 visite)
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Impact Factor: 4.556
Dettagli Esporta in BibTeX Esporta in EndNote
Fik-jaskółka MA, Mkrtchyan AF, Saghyan AS, Palumbo R, Belter A, Hayriyan LA, Simonyan H, Roviello V, Roviello GN
* Spectroscopic and SEM evidences for G4-DNA binding by a synthetic alkyne-containing amino acid with anticancer activity (177 visite) (PDF 68 visite)
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Impact Factor: 3.232
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Granato L, Longo D, Boutry S, Vander Elst L, Henoumont C, Aime S, Muller RN, Laurent S
* Synthesis and Relaxometric Characterization of New Poly[N, N-bis(3-aminopropyl)glycine] (PAPGly) Dendrons Gd-Based Contrast Agents and Their in Vivo Study by Using the Dynamic Contrast-Enhanced MRI Technique at Low Field (1 T) (119 visite)
Chem Biodivers (ISSN: 1612-1872linking), 2019 Nov; 16(11): e1900322-e1900322.
Impact Factor: 1.449
Dettagli Esporta in BibTeX Esporta in EndNote
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* MRI features suggestive of gadolinium retention do not correlate with Expanded Disability Status Scale worsening in Multiple Sclerosis (267 visite)
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Impact Factor: 1.287
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* Oil Core-PEG Shell Nanocarriers for In Vivo MRI Imaging (166 visite)
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* Gadolinium Retention in the Rat Brain: Assessment of the Amounts of Insoluble Gadolinium-containing Species and Intact Gadolinium Complexes after Repeated Administration of Gadolinium-based Contrast Agents (270 visite)
Radiology (ISSN: 0033-8419, 1527-1315), 2017 Dec; 285(3): 839-849.
Impact Factor: 7.469
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Tomasello MF, Nardon C, Lanza V, Di Natale G, Pettenuzzo N, Salmaso S, Milardi D, Caliceti P, Pappalardo G, Fregona D
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* Cancer-selective targeting of the NF-kappaB survival pathway with GADD45beta/MKK7 inhibitors (566 visite)
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Impact Factor: 23.523
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Impact Factor: 4.383
Dettagli Esporta in BibTeX Esporta in EndNote
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* Imaging of thyroid tumor angiogenesis with microbubbles targeted to vascular endothelial growth factor receptor type 2 in mice (437 visite)
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Brain (ISSN: 0006-8950, 1460-2156electronic, 0006-8950linking), 2012 Sep; 135(Pt9): 2817-2825.
Impact Factor: 9.915
Dettagli Esporta in BibTeX Esporta in EndNote
Digilio G, Menchise V, Gianolio E, Catanzaro V, Carrera C, Napolitano R, Fedeli F, Aime S
* Exofacial protein thiols as a route for the internalization of Gd(III)-based complexes for magnetic resonance imaging cell labeling (430 visite)
J Med Chem (ISSN: 0022-2623, 1520-4804, 0022-2623print), 2010 Jul 8; 53(13): 4877-4890.
Impact Factor: 5.207
Dettagli Esporta in BibTeX Esporta in EndNote
Berkouk K, Quarantelli M, Prinster A, Landeau B, Alfano B, Baron JC
* Mapping The Relative Contribution Of Gray Matter Activity Versus Volume In Brain Pet. A New Approach (346 visite) (PDF 216 visite)
J Neuroimaging (ISSN: 1051-2284), 2006 Jul; 16(3): 224-235.
Impact Factor: 1.298
Dettagli Esporta in BibTeX Esporta in EndNote
Aloj L, Panico M, Caraco C, Del Vecchio S, Arra C, Affuso A, Accardo A, Mansi R, Tesauro D, De Luca S, Pedone C, Visentin R, Mazzi U, Morelli G, Salvatore M
* In vitro and in vivo characterization of Indium-111 and Technetium-99m labeled CCK-8 derivatives for CCK-B receptor imaging (462 visite)
Cancer Biotherapy And Radiopharmaceuticals (ISSN: 1084-9785, 1084-4978), 2004 Feb; 19(1): 93-98.
Impact Factor: 1.091
Dettagli Esporta in BibTeX Esporta in EndNote
Andretta C, Catalano L, Pace L, Fonti R, Annunziata G, Rotoli B
* 99mTc-sestaMIBI scintigraphy in thalidomide-treated refractory or relapsed multiple myeloma patients [2] (272 visite)
Leuk Lymphoma (ISSN: 1042-8194, 1026-8022linking), 2003 Jun; 44(6): 1081-1082.
Impact Factor: 1.163
Dettagli Esporta in BibTeX Esporta in EndNote
Maurea S, Lastoria S, Caracò C, Klain M, Varrella P, Acampa W, Muto P, Salvatore M
The role of radiolabeled somatostatin analogs in adrenal imaging (310 visite)
Nucl Med Biol (ISSN: 0969-8051, 0883-2897), 1996 Sep; 23(6): 677-680.
Impact Factor: 1.042
Dettagli Esporta in BibTeX Esporta in EndNote
Trischitta V, Benzi L, Brunetti A, Cecchetti P, Marchetti P, Vigneri R, Navalesi R
Intracellular insulin processing is altered in monocytes from patients with type II diabetes mellitus (900 visite)
J Clin Endocrinol Metab (ISSN: 0021-972x), 1987 May; 64(5): 914-920.
Impact Factor: 4.575
Dettagli Esporta in BibTeX Esporta in EndNote
24 Records (24 escludendo Abstract e Conferenze).
Impact factor totale: 119.663 (119.663 escludendo Abstract e Conferenze).
Impact factor a 5 anni totale: 127.623 (127.623 escludendo Abstract e Conferenze).
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