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dc.contributor.author
Iezzi, Maria Elena
dc.contributor.author
Policastro, Lucia Laura
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Werbajh, Santiago Enrique
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Podhajcer, Osvaldo Luis
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Canziani, Gabriela Alicia
dc.date.available
2019-12-02T19:38:24Z
dc.date.issued
2018-02
dc.identifier.citation
Iezzi, Maria Elena; Policastro, Lucia Laura; Werbajh, Santiago Enrique; Podhajcer, Osvaldo Luis; Canziani, Gabriela Alicia; Single-domain antibodies and the promise of modular targeting in cancer imaging and treatment; Frontiers Research Foundation; Frontiers in Immunology; 9; FEB; 2-2018; 1-11
dc.identifier.issn
1664-3224
dc.identifier.uri
http://hdl.handle.net/11336/91107
dc.description.abstract
Monoclonal antibodies and their fragments have significantly changed the outcome of cancer in the clinic, effectively inhibiting tumor cell proliferation, triggering antibody-dependent immune effector cell activation and complement mediated cell death. Along with a continued expansion in number, diversity, and complexity of validated tumor targets there is an increasing focus on engineering recombinant antibody fragments for lead development. Single-domain antibodies (sdAbs), in particular those engineered from the variable heavy-chain fragment (VHH gene) found in Camelidae heavy-chain antibodies (or IgG2 and IgG3), are the smallest fragments that retain the full antigen-binding capacity of the antibody with advantageous properties as drugs. For similar reasons, growing attention is being paid to the yet smaller variable heavy chain new antigen receptor (VNAR) fragments found in Squalidae. sdAbs have been selected, mostly from immune VHH libraries, to inhibit or modulate enzyme activity, bind soluble factors, internalize cell membrane receptors, or block cytoplasmic targets. This succinct review is a compilation of recent data documenting the application of engineered, recombinant sdAb in the clinic as epitope recognition "modules" to build monomeric, dimeric and multimeric ligands that target, tag and stall solid tumor growth in vivo. Size, affinity, specificity, and the development profile of sdAbs drugs are seemingly consistent with desirable clinical efficacy and safety requirements. But the hepatotoxicity of the tetrameric anti-DR5-VHH drug in patients with pre-existing anti-drug antibodies halted the phase I clinical trial and called for a thorough pre-screening of the immune and poly-specific reactivities of the sdAb leads.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Frontiers Research Foundation
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
BIOAVAILABILITY
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BROAD EPITOPE COVERAGE
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CAMELID HEAVY-CHAIN ANTIBODY
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DRUG-LIKE PROPERTIES
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IMMUNOGENICITY
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POLY-SPECIFICITY
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Oncología
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Medicina Clínica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Single-domain antibodies and the promise of modular targeting in cancer imaging and treatment
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2019-10-22T17:46:53Z
dc.journal.volume
9
dc.journal.number
FEB
dc.journal.pagination
1-11
dc.journal.pais
Suiza
dc.description.fil
Fil: Iezzi, Maria Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
dc.description.fil
Fil: Policastro, Lucia Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Comisión Nacional de Energía Atómica; Argentina
dc.description.fil
Fil: Werbajh, Santiago Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
dc.description.fil
Fil: Podhajcer, Osvaldo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
dc.description.fil
Fil: Canziani, Gabriela Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
dc.journal.title
Frontiers in Immunology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.3389/fimmu.2018.00273
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fimmu.2018.00273/full
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