モノクローナル抗体を用いたアクアポリン3を標的としたがん治療法の開発

• Published in: 日本薬理学会年会要旨集 p. 3-P-280
• Main Authors: 竹馬, 真理子, 田中, 愛美
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2022
• Subjects: antibody; cancer
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.95.0_3-P-280

Aquaporin-3 (AQP3), a member of the water- and small molecule-transporting protein family, is involved in inflammatory disease and cancer progression. Its role in pathogenesis has been attributed to AQP3-mediated H2O2 or glycerol transport.In this study, we showed that a recently established anti-AQP3 monoclonal antibody (mAb) suppresses tumor growth in allograft mouse tumor models. Administration of the anti-AQP3 mAb increased the M1/M2 ratio of tumor-associated macrophages (TAM) and improved the mitochondrial function of T cells in the tumor microenvironment (TME). In an in vitro study, the anti-AQP3 mAb attenuated carcinoma cell-mediated polarization of monocytes into M2-like TAMs and enhanced the cellular energy metabolism of M1 macrophages, thereby decreasing the immunosuppressive profile of TAMs. Administration of anti-AQP3 mAb also restored the TAM-induced decrease in T cell proliferation. Macrophage depletion counteracted the antitumor effect of anti-AQP3 mAb in mouse tumor models, indicating that the primary targets of anti-AQP3 mAb are macrophages.These data suggest that anti-AQP3 mAb suppresses tumor growth by attenuating immunosuppressive M2-like TAMs, which in turn maintains the antitumor function of T cells in the TME. Thus, the anti-AQP3 mAb is a potential cancer therapy that functions by targeting TAMs.