[Anti-CCR4 mAb and regulatory T cells]

Despite receiving multidisciplinary therapy, patients with advanced or recurrent cancer experience poor survival. Therefore, novel and effective therapies should be developed. In various malignancies, tumor cells can evade the host immune defenses, in which CD4+CD25+ regulatory Tcells (Treg) play an important role. Tregs maintain self-tolerance and homeostasis in the immune system, thereby suppressing the antitumor immune responses in cancer patients. Thus, Tregs are crucial in controlling antitumor immune responses. Several clinical studies have shown that the presence of Tregs at the tumor site was correlated with poor prognosis, and Tregs reportedly suppress the antigen-specific T-cell induction in immunotherapy. Therefore, controlling Treg function may be a promising immunotherapy. Based on the findings of adult T-cell leukemia-lymphoma research, Tregs have been shown to display high cell-surface expression of the CC chemokine receptor, CCR4. The anti-CCR4 monoclonal antibody recognizes the CCR4 molecule and induces robust ADCC activity against CCR4-positive cells such as Tregs. Thus, Treg depletion using humanized anti-CCR4 monoclonal antibodies may enhance the host immune response against tumors. The current ongoing clinical trial investigates the use of humanized anti-human-CCR4 monoclonal antibody, mogamulizumab, in the treatment of advanced solid tumors.