Combined targeting of costimulatory (OX40) and coinhibitory (CTLA-4) pathways elicits potent effector T cells capable of driving robust antitumor immunity.

ABSTRACT: Ligation of the TNF receptor family costimulatory molecule OX40 (CD134) with an agonist anti-OX40 monoclonal antibody (mAb) enhances antitumor immunity by augmenting T-cell differentiation as well as turning off the suppressive activity of the FoxP3(+)CD4(+) regulatory T cells (Treg). In addition, antibody-mediated blockade of the checkpoint inhibitor CTLA-4 releases the "brakes" on T cells to augment tumor immunotherapy. However, monotherapy with these agents has limited therapeutic benefit particularly against poorly immunogenic murine tumors. Therefore, we examined whether the administration of agonist anti-OX40 therapy in the presence of CTLA-4 blockade would enhance tumor immunotherapy. Combined anti-OX40/anti-CTLA-4 immunotherapy significantly enhanced tumor regression and the surviv

SUBMITTER: Redmond WL 

PROVIDER: S-EPMC4007342 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature