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dc.creatorSuarez, N. (Natalia)-
dc.creatorAlfaro, C. (Carlos)-
dc.creatorDubrot, J. (Juan)-
dc.creatorPalazon, A. (Asís)-
dc.creatorBolaños, E. (Elixabet)-
dc.creatorErro, L. (Lorena)-
dc.creatorHervas-Stubbs, S. (Sandra)-
dc.creatorMartinez-Forero, I. (Iván)-
dc.creatorMorales-Kastresana, A. (Aizea)-
dc.creatorMartin-Algarra, S. (Salvador)-
dc.creatorSangro, B. (Bruno)-
dc.creatorLecanda, F. (Fernando)-
dc.creatorPerez-Gracia, J.L. (Jose Luis)-
dc.creatorGonzalez-Hernandez, A. (Alvaro)-
dc.creatorMelero, I. (Ignacio)-
dc.identifier.citationSuarez 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.description.abstractAnti-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.subjectT celles_ES
dc.subjectRegulatory T cellses_ES
dc.subjectDendritic celles_ES
dc.titleSynergistic effects of CTLA-4 blockade with tremelimumab and elimination of regulatory T lymphocytes in vitro and in vivoes_ES

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