A humanized, Fc disabled anti-human glucocorticoid-induced tumor necrosis factor receptor (GITR) monoclonal antibody (MoAb) with immunomodulating activity. Anti-human GITR MoAb TRX518 blocks the interaction of GITR, found on multiple types of T cells, with its ligand, thereby inducing both the activation of tumor-antigen-specific T effector cells, as well as abrogating the suppression induced by inappropriately activated T regulatory cells. This agent is shown to act synergistically with chemotherapeutic drugs in multiple cancer models.