Full metadata record
DC Field | Value | Language |
---|---|---|
dc.creator | Suarez, N. (Natalia) | - |
dc.creator | Alfaro, C. (Carlos) | - |
dc.creator | Dubrot, J. (Juan) | - |
dc.creator | Palazon, A. (Asís) | - |
dc.creator | Bolaños, E. (Elixabet) | - |
dc.creator | Erro, L. (Lorena) | - |
dc.creator | Hervas-Stubbs, S. (Sandra) | - |
dc.creator | Martinez-Forero, I. (Iván) | - |
dc.creator | Morales-Kastresana, A. (Aizea) | - |
dc.creator | Martin-Algarra, S. (Salvador) | - |
dc.creator | Sangro, B. (Bruno) | - |
dc.creator | Lecanda, F. (Fernando) | - |
dc.creator | Perez-Gracia, J.L. (Jose Luis) | - |
dc.creator | Gonzalez-Hernandez, A. (Alvaro) | - |
dc.creator | Melero, I. (Ignacio) | - |
dc.date.accessioned | 2012-04-26T08:53:56Z | - |
dc.date.available | 2012-04-26T08:53:56Z | - |
dc.date.issued | 2011 | - |
dc.identifier.citation | Suarez N, Alfaro C, Dubrot J, Palazon A, Bolanos E, Erro L, et al. Synergistic effects of CTLA-4 blockade with tremelimumab and elimination of regulatory T lymphocytes in vitro and in vivo. Int J Cancer 2011 Jul 15;129(2):374-386. | es_ES |
dc.identifier.issn | 1097-0215 | - |
dc.identifier.uri | https://hdl.handle.net/10171/21806 | - |
dc.description.abstract | Anti-CTLA-4 monoclonal antibodies (mAb) that block the interaction of CTLA-4 with CD80 and CD86 such as tremelimumab and ipilimumab are currently being tested in the clinic for cancer treatment exploiting their properties to de-repress tumor-specific cellular immunity. Addition of the fully human anti-CTLA-4 (tremelimumab) to cultures of human T cells with allogenic dendritic cells (DCs) did not increase proliferation. Magnetic bead-mediated elimination of CD4(+) CD25(+) regulatory T cells (T(reg)) before setting up those alloreactive cultures also largely failed to increase primary proliferation. In contrast, predepletion of CD4(+) CD25(+) T(reg) and culture in the presence of tremelimumab synergistically resulted in increased proliferation and DC:T-cell aggregation. These effects were much more prominent in CD4 than in CD8 T cells. The synergy mechanism can be traced to enhanced CTLA-4 expression in effector cells as a result of T(reg) elimination, thereby offering more targets to the blocking antibody. Human T cells and allogenic DCs (derived both from healthy donors and advanced cancer patients) were coinjected in the peritoneum of Rag2(-/-) IL-2Rγ(-/-) mice. In these conditions, tremelimumab injected intravenously did not significantly enhance alloreactive proliferation unless T(reg) cells had been predepleted. Synergistic effects in vivo were again largely restricted to the CD4 T-cell compartment. In addition, T(reg) depletion and CTLA-4 blockade synergistically enhanced specific cytotoxicity raised in culture against autologous EBV-transformed cell lines. Taken together, these experiments indicate that tremelimumab therapy may benefit from previous or concomitant T(reg) depletion. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Wiley-Blackwell | es_ES |
dc.rights | info:eu-repo/semantics/closedAccess | - |
dc.subject | CTLA-4 | es_ES |
dc.subject | T cell | es_ES |
dc.subject | Regulatory T cells | es_ES |
dc.subject | Dendritic cell | es_ES |
dc.subject | Tremelimumab | es_ES |
dc.title | Synergistic effects of CTLA-4 blockade with tremelimumab and elimination of regulatory T lymphocytes in vitro and in vivo | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.relation.publisherversion | http://bit.ly/JFBTOO | es_ES |
dc.type.driver | info:eu-repo/semantics/article | es_ES |
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