Abstract
Background: Human epidermal growth factor receptor 3 (HER3) has been found to be overexpressed in many cancers such as lung, breast, and colon cancers. High expression of HER3 is thought to be a negative prognostic factor in several solid tumors including colorectal cancer. Moreover, HER3 is associated with drug resistance to EGFR- and HER2-targeted therapy in some cancers. Therefore, HER3 is thought to be an important therapeutic target.
Purpose: We aimed to develop a novel anti-HER3 monoclonal antibody (mAb), and investigated its antitumor activities against colorectal cancer.
Methods: We employed the Cell-Based Immunization and Screening (CBIS) method using HER3-overexpressed CHO-K1 cells for producing anti-HER3 mAbs. Anti-HER3 mAbs were screened using flow cytometry (FCM). Then, we examined the antibody‑dependent cellular cytotoxicity (ADCC) and the complement‑dependent cytotoxicity (CDC) activities of anti-HER3 mAbs for Caco‑2 (a human colorectal adenocarcinoma cell line). Moreover, a mouse xenograft model of Caco-2 was used for examining the antitumor activity.
Results: We developed an anti-HER3 mAbs, H3Mab-17 (IgG2a, kappa) using CBIS method. H3Mab-17 reacted with HER3-expressing cells in FCM. In vitro analysis demonstrated that H3Mab-17 showed the ADCC and CDC activities against Caco-2. H3Mab-17 significantly reduced tumor development in Caco-2 xenograft compared with control mouse IgG.
Conclusion: We have successfully established a novel anti-HER3 mAb (H3Mab-17), which could be a useful antibody-based therapy for patients with HER3-expressing colorectal cancers.
