Purpose: FoxP3+ Tregs inhibit immune responses against tumors. KW-0761 is a humanized anti-human CCR4 monoclonal antibody (mAb) that has ADCC activity. Depletion of CCR4-expressing FoxP3+ CD4 Tregs by KW-0761 infusion was investigated in solid cancer patients.
Experimental Design: We conducted a phase Ia clinical trial of KW-0761 infusion in 7 lung and 3 esophageal cancer patients. Toxicity, clinical efficacy, changes in lymphocyte subpopulations, including Tregs, and induction of immune responses were analyzed.
Results: The results showed that KW-0761 infusion at dose range between 0.1 mg/kg to 1.0 mg/kg was safe and well tolerated. No DLT was observed. Four of 10 patients showed stable disease during treatment and were long survivors. The monitoring of FoxP3+ Tregs in the PBMCs during treatment indicated efficient depletion of those cells even at the lowest dose of 0.1 mg/kg used. The reduction in Th 1 CD4 T-cells and CD8 T-cells was limited, while a significant reduction was observed with Th 2 and Th 17 CD4 T-cells. Immune responses to cancer/testis (CT) antigens and an autoantibody response to thyroid peroxidase were observed in some patients.
Conclusions: The findings showed Tregs depletion and the possible occurrence of an immune response following KW-0761 infusion. Combined use of KW-0761 to deplete FoxP3+ Tregs with other immunotherapies, such as cancer vaccines or checkpoint inhibitors, is promising to augment immune responses.
Citation Format: Koji Kurose, Yoshihiro Ohue, Hisashi Wada, Toshihiko Doi, Hiroyoshi Nishikawa, Mikio Oka, Ryuzo Ueda. Phase Ia study of FoxP3+ CD4 Treg depletion by infusion of a humanized anti-CCR4 antibody, KW-0761, in cancer patients. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr A033.
- ©2016 American Association for Cancer Research.