Full metadata record
DC Field | Value | Language |
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dc.creator | Compte, M. (Marta) | - |
dc.creator | Harwood, S.L. (Seandean Lykke) | - |
dc.creator | Muñoz, I.G. (Inés G.) | - |
dc.creator | Navarro, R. (Rocío) | - |
dc.creator | Zonca, M. (Manuela) | - |
dc.creator | Pérez-Chacon, G. (Gema) | - |
dc.creator | Erce-Llamazares, A. (Ainhoa) | - |
dc.creator | Merino, N. (Nekane) | - |
dc.creator | Tapia-Galisteo, A. (Alberto) | - |
dc.creator | Cuesta, A.M. (Ángel M.) | - |
dc.creator | Mikkelsen, K. (Kasper) | - |
dc.creator | Caleiras, E. (Eduardo) | - |
dc.creator | Núñez-Prado, N. (Natalia) | - |
dc.creator | Aznar, M.A. (María Ángela) | - |
dc.creator | Lykkemark, S. (Simon) | - |
dc.creator | Martínez-Torrecuadrada, J. (Jorge) | - |
dc.creator | Melero, I. (Ignacio) | - |
dc.creator | Blanco, F.J. (Francisco J.) | - |
dc.creator | Serna, J.B. (Jorge Bernardino) de la | - |
dc.creator | Zapata, J.M. (Juan M.) | - |
dc.creator | Sanz, L. (Laura) | - |
dc.creator | Álvarez-Vallina, L. (Luis) | - |
dc.date.accessioned | 2018-12-11T10:45:42Z | - |
dc.date.available | 2018-12-11T10:45:42Z | - |
dc.date.issued | 2018 | - |
dc.identifier.citation | Compte, M.; Harwood, S. L.; Munoz, I. G.; et al. "A tumor-targeted trimeric 4-1BB-agonistic antibody induces potent anti-tumor immunity without systemic toxicity". Nature communications. 9 (1), 2018, 4809 | es |
dc.identifier.issn | 2041-1723 | - |
dc.identifier.uri | https://hdl.handle.net/10171/56004 | - |
dc.description.abstract | The costimulation of immune cells using first-generation anti-4-1BB monoclonal antibodies (mAbs) has demonstrated anti-tumor activity in human trials. Further clinical development, however, is restricted by significant off-tumor toxicities associated with Fc gamma R interactions. Here, we have designed an Fc-free tumor-targeted 4-1BB-agonistic trimerbody, 1D8(N)/(C)EGa1, consisting of three anti-4-1BB single-chain variable fragments and three anti-EGFR single-domain antibodies positioned in an extended hexagonal conformation around the collagen XVIII homotrimerization domain. The1D8(N)/(C)EGa1 trimerbody demonstrated high-avidity binding to 4-1BB and EGFR and a potent in vitro costimulatory capacity in the presence of EGFR. The trimerbody rapidly accumulates in EGFR-positive tumors and exhibits anti-tumor activity similar to IgG-based 4-1BB-agonistic mAbs. Importantly, treatment with 1D8(N)/(C)EGa1 does not induce systemic inflammatory cytokine production or hepatotoxicity associated with IgG-based 4-1BB agonists. These results implicate Fc gamma R interactions in the 4-1BB-agonist-associated immune abnormalities, and promote the use of the non-canonical antibody presented in this work for safe and effective costimulatory strategies in cancer immunotherapy. | - |
dc.language.iso | en | - |
dc.relation | info:eu-repo/grantAgreement/EC/FP7/618914/EU | - |
dc.relation | info:eu-repo/grantAgreement/EC/H2020/653706/EU | - |
dc.relation | info:eu-repo/grantAgreement/EC/FP7/602262/EU | - |
dc.rights | info:eu-repo/semantics/openAccess | - |
dc.subject | 4-1bb costimulation | - |
dc.subject | Monoclonal-antibodies | - |
dc.subject | In-vivo | - |
dc.subject | Anti-cd137 mab | - |
dc.subject | T-cells | - |
dc.subject | Cancer | - |
dc.subject | Immunotherapy | - |
dc.subject | Cd137 | - |
dc.subject | Stimulation | - |
dc.subject | Induction | - |
dc.title | A tumor-targeted trimeric 4-1BB-agonistic antibody induces potent anti-tumor immunity without systemic toxicity | - |
dc.type | info:eu-repo/semantics/article | - |
dc.relation.publisherversion | https://www.ncbi.nlm.nih.gov/pubmed/?term=A+tumor-targeted+trimeric+4-1BB-agonistic+antibody+induces+potent+anti-tumor+immunity+without+systemic+toxicity | - |
dc.description.note | This is an open access article distributed under the Creative Commons: Atribution License (cc BY) | - |
dc.identifier.doi | 10.1038/s41467-018-07195-w | - |
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