Tomohiro Tanaka1, Tomokazu Ohishi2, Teizo Asano1, Junko Takei1, Ren Nanamiya1, Hideki Hosono1, Masato Sano1, Hiroyuki Harada3, Manabu Kawada2, Mika K Kaneko1, Yukinari Kato1. 1. Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, Aoba‑ku, Sendai, Miyagi 980‑8575, Japan. 2. Institute of Microbial Chemistry (BIKAKEN), Numazu, Microbial Chemistry Research Foundation, Numazu‑shi, Shizuoka 410‑0301, Japan. 3. Department of Oral and Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo‑ku, Tokyo 113‑8510, Japan.
Abstract
Trophoblast cell surface antigen 2 (TROP2), reported to be overexpressed in several types of cancer, is involved in cell proliferation, invasion, metastasis, and poor prognosis of many types of cancer. Previously, a highly sensitive anti‑TROP2 monoclonal antibody (clone TrMab‑6; mouse IgG2b, κ) was developed using a Cell‑Based Immunization and Screening (CBIS) method. TrMab‑6 was useful for investigations using flow cytometry, western blot, and immunohistochemistry. The aim of the present study was to investigate whether TrMab‑6 possesses in vitro antibody‑dependent cellular cytotoxicity (ADCC) or complement‑dependent cytotoxicity (CDC) activities or in vivo antitumor activities using mouse xenograft models of TROP2‑overexpressed CHO‑K1 (CHO/TROP2) and breast cancer cell lines, including MCF7, MDA‑MB‑231, and MDA‑MB‑468. In vitro experiments revealed that TrMab‑6 strongly induced ADCC and CDC activities against CHO/TROP2 and the three breast cancer cell lines, whereas it did not show those activities against parental CHO‑K1 and MCF7/TROP2‑knockout cells. Furthermore, in vivo experiments on CHO/TROP2 and MCF7 xenografts revealed that TrMab‑6 significantly reduced tumor growth, whereas it did not show antitumor activities against parental CHO‑K1 and MCF7/TROP2‑knockout xenografts. The findings suggest that TrMab‑6 is a promising treatment option for TROP2‑expressing breast cancers.
Trophoblast cell surface antigen 2 (pan class="Gene">TROP2), reported to be overexpressed in several types of n>n class="Disease">cancer, is involved in cell proliferation, invasion, metastasis, and poor prognosis of many types of cancer. Previously, a highly sensitive anti‑TROP2 monoclonal antibody (clone TrMab‑6; mouseIgG2b, κ) was developed using a Cell‑Based Immunization and Screening (CBIS) method. TrMab‑6 was useful for investigations using flow cytometry, western blot, and immunohistochemistry. The aim of the present study was to investigate whether TrMab‑6 possesses in vitro antibody‑dependent cellular cytotoxicity (ADCC) or complement‑dependent cytotoxicity (CDC) activities or in vivo antitumor activities using mouse xenograft models of TROP2‑overexpressed CHO‑K1 (CHO/TROP2) and breast cancer cell lines, including MCF7, MDA‑MB‑231, and MDA‑MB‑468. In vitro experiments revealed that TrMab‑6 strongly induced ADCC and CDC activities against CHO/TROP2 and the three breast cancer cell lines, whereas it did not show those activities against parental CHO‑K1 and MCF7/TROP2‑knockout cells. Furthermore, in vivo experiments on CHO/TROP2 and MCF7 xenografts revealed that TrMab‑6 significantly reduced tumor growth, whereas it did not show antitumor activities against parental CHO‑K1 and MCF7/TROP2‑knockout xenografts. The findings suggest that TrMab‑6 is a promising treatment option for TROP2‑expressing breast cancers.
Entities:
Keywords:
ADCC; CDC; TROP2; antitumor activity; breast cancer; monoclonal antibody