Pegylated Trastuzumab Fragments Acquire an Increased in Vivo Stability but Show a Largely Reduced Affinity for the Target Antigen (466 views) (PDF public 264 views)
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: Journal Article,
Impact factor: 3.226, 5-year impact factor: 3.482
Url: https://www.scopus.com/inward/record.uri?eid=2-s2.0-84962385296&doi=10.3390%2fijms17040491&partnerID=40&md5=35ef6085d9521fc0431927bb55bd407e
Keywords: Fab, Pegylation, Antibody Fragment, Papain Digestion, Pepsin Digestion, Pharmacokinetics,
Affiliations:
*** 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:
Not available.
Int J Mol Sc (ISSN: 1422-0067, 1661-6596, 1422-0067linking), 2016 Apr 1; 17(4): N/D-N/D.
Export to BibTeX Export to EndNote
Paper type: Journal Article,
Impact factor: 3.226, 5-year impact factor: 3.482
Url: https://www.scopus.com/inward/record.uri?eid=2-s2.0-84962385296&doi=10.3390%2fijms17040491&partnerID=40&md5=35ef6085d9521fc0431927bb55bd407e
Keywords: Fab, Pegylation, Antibody Fragment, Papain Digestion, Pepsin Digestion, Pharmacokinetics,
Affiliations:
*** 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:
Not available.
Pegylated Trastuzumab Fragments Acquire an Increased in Vivo Stability but Show a Largely Reduced Affinity for the Target Antigen
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
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Pegylated Trastuzumab Fragments Acquire an Increased in Vivo Stability but Show a Largely Reduced Affinity for the Target Antigen
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View Export to BibTeX Export to EndNote
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* In vivo imaging and characterization of [(18)F]DPA-714, a potential new TSPO ligand, in mouse brain and peripheral tissues using small-animal PET (911 views) (PDF 298 views)
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View Export to BibTeX Export to EndNote
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Impact Factor: 0.983
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Pascual B, Prieto E, Arbizu J, Marti-climent JM, Penuelas I, Quincoces G, Zarauza R, Pappata S, Masdeu JC
* Decreased carbon-11-flumazenil binding in early Alzheimer's disease (477 views) (PDF 297 views)
Brain (ISSN: 0006-8950, 1460-2156electronic, 0006-8950linking), 2012 Sep; 135(Pt9): 2817-2825.
Impact Factor: 9.915
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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 (571 views)
J Med Chem (ISSN: 0022-2623, 1520-4804, 0022-2623print), 2010 Jul 8; 53(13): 4877-4890.
Impact Factor: 5.207
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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 (628 views) (PDF 254 views)
J Neuroimaging (ISSN: 1051-2284, 1051-2284linking), 2006 Jul; 16(3): 224-235.
Impact Factor: 1.298
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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 (668 views)
Cancer Biotherapy And Radiopharmaceuticals (ISSN: 1084-9785, 1084-4978), 2004 Feb; 19(1): 93-98.
Impact Factor: 1.091
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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] (396 views)
Leuk Lymphoma (ISSN: 1042-8194, 1026-8022linking), 2003 Jun; 44(6): 1081-1082.
Impact Factor: 1.163
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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 (519 views)
Nucl Med Biol (ISSN: 0969-8051, 0883-2897), 1996 Sep; 23(6): 677-680.
Impact Factor: 1.042
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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 (1104 views)
J Clin Endocrinol Metab (ISSN: 0021-972x), 1987 May; 64(5): 914-920.
Impact Factor: 4.575
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26 Records (25 excluding Abstracts).
Total impact factor: 122.092 (121.001 excluding Abstracts).
Total 5 year impact factor: 129.922 (128.237 excluding Abstracts).
Total impact factor: 122.092 (121.001 excluding Abstracts).
Total 5 year impact factor: 129.922 (128.237 excluding Abstracts).
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