TY - JOUR
T1 - Anti-her3 monoclonal antibody exerts antitumor activity in a mouse model of colorectal adenocarcinoma
AU - ASANO, TEIZO
AU - OHISHI, TOMOKAZU
AU - TAKEI, JUNKO
AU - NAKAMURA, TAKURO
AU - NANAMIYA, REN
AU - HOSONO, HIDEKI
AU - TANAKA, TOMOHIRO
AU - Sano, Masato
AU - HARADA, HIROYUKI
AU - KAWADA, MANABU
AU - KANEKO, MIKA K.
AU - KATO, YUKINARI
N1 - Funding Information:
This research was supported in part by the Japan Agency for Medical Research and Development (AMED) under grant nos. JP21am0401013 (to YK) and JP21am0101078 (to YK), and by the Japan Society for the Promotion of Science (JSPS) Grants‑in‑Aid for Scientific Research (KAKENHI) grant nos. 21K15523 (to TA), 21K07168 (to MKK), 19K07705 (to YK) and 20K16322 (to MS).
Funding Information:
Construction of plasmids. The Genome Network Project clone IRAK174J18 (HER3) was provided by the RIKEN BioResource Research Center through the National BioResource Project of the MEXT and AMED agencies of Japan. HER3 DNA plus N‑terminal PA16 tag, recognized by NZ‑1, was subcloned into a pCAG‑Ble vector (FUJIFILM Wako Pure Chemical Corp.) and named pCAG/PA16‑HER3. HER3 DNA plus C‑terminal PA tag, recognized by NZ‑1, was subcloned into a pCAG‑Neo vector (FUJIFILM Wako Pure Chemical Corp.) and named pCAG/HER3‑PA.
Publisher Copyright:
© 2021 Spandidos Publications. All rights reserved.
PY - 2021/8
Y1 - 2021/8
N2 - HER3 belongs to the epidermal growth factor receptor (EGFR) family and is known to form an active heterodimer with other three family members EGFR, HER2, and HER4. HER3 is overexpressed in lung, breast, colon, prostate, and gastric cancers. In the present study, we developed and validated an anti-HER3 monoclonal antibody (mAb), H3Mab-17 (IgG2a, kappa), by immunizing mice with HER3-overexpressed CHO-K1 cells (CHO/HER3). H3Mab-17 was found to react specifically with endogenous HER3 in colorectal carcinoma cell lines, using flow cytometry. The KD for H3Mab-17 in CHO/HER3 and Caco-2 (a colon cancer cell line) were determined to be 3.0x10-9 M and 1.5x10-9 M via flow cytometry, respectively, suggesting high binding affinity of H3Mab-17 to HER3. Then, we assessed the H3Mab-17 antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against Caco-2, and evaluated its antitumor capacity in a Caco-2 xenograft model. In vitro experiments revealed H3Mab-17 had strongly induced both ADCC and CDC against Caco-2 cells. In vivo experiments on Caco-2 xenografts revealed that H3Mab-17 treatment significantly reduced tumor growth compared with the control mouse IgG. These data indicated that H3Mab-17 could be a promising treatment option for HER3-expressing colon cancers.
AB - HER3 belongs to the epidermal growth factor receptor (EGFR) family and is known to form an active heterodimer with other three family members EGFR, HER2, and HER4. HER3 is overexpressed in lung, breast, colon, prostate, and gastric cancers. In the present study, we developed and validated an anti-HER3 monoclonal antibody (mAb), H3Mab-17 (IgG2a, kappa), by immunizing mice with HER3-overexpressed CHO-K1 cells (CHO/HER3). H3Mab-17 was found to react specifically with endogenous HER3 in colorectal carcinoma cell lines, using flow cytometry. The KD for H3Mab-17 in CHO/HER3 and Caco-2 (a colon cancer cell line) were determined to be 3.0x10-9 M and 1.5x10-9 M via flow cytometry, respectively, suggesting high binding affinity of H3Mab-17 to HER3. Then, we assessed the H3Mab-17 antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against Caco-2, and evaluated its antitumor capacity in a Caco-2 xenograft model. In vitro experiments revealed H3Mab-17 had strongly induced both ADCC and CDC against Caco-2 cells. In vivo experiments on Caco-2 xenografts revealed that H3Mab-17 treatment significantly reduced tumor growth compared with the control mouse IgG. These data indicated that H3Mab-17 could be a promising treatment option for HER3-expressing colon cancers.
KW - Antibody-dependent cellular cytotoxicity
KW - Antitumor activity
KW - Colorectal cancer
KW - Complement-dependent cytotoxicity
KW - HER3
KW - Monoclonal antibody
UR - http://www.scopus.com/inward/record.url?scp=85109697529&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85109697529&partnerID=8YFLogxK
U2 - 10.3892/OR.2021.8124
DO - 10.3892/OR.2021.8124
M3 - Article
C2 - 34184091
AN - SCOPUS:85109697529
VL - 46
JO - Oncology Reports
JF - Oncology Reports
SN - 1021-335X
IS - 2
M1 - 8124
ER -
