H2Mab-19, an anti-human epidermal growth factor receptor 2 monoclonal antibody exerts antitumor activity in mouse oral cancer xenografts.

Junko Takei,Manabu Kawada,Yukinari Kato,Tomokazu Ohishi,Mika Kaneko,Hiroyuki Harada

doi:10.3892/etm.2020.8765

Abstract

Human epidermal growth factor receptor 2 (HER2) is reported to be overexpressed in breast cancers and is associated with poor clinical outcome. Trastuzumab is a humanized anti-HER2 antibody that offers significant survival benefits to patients with HER2-overexpressing breast cancer. In this study, a novel anti-HER2 monoclonal antibody (mAb), H2Mab-19 (IgG2b, kappa) was developed. Antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and antitumor activity of H2Mab-19 were investigated using both breast cancer and oral cancer cell lines. H2Mab-19 demonstrated cytotoxicity in BT-474 (a human breast cancer cell line) and HSC-2 or SAS (human oral cancer cell lines). H2Mab-19 also possessed both ADCC and CDC activity against BT-474, HSC-2, and SAS cell lines. In comparison to control mouse IgG, H2Mab-19 significantly reduced tumor development in BT-474, HSC-2, and SAS xenografts. Collectively, these results suggest that treatment with H2Mab-19 may be a useful therapy for patients with HER2-expressing breast and oral cancers.

Highlights

The overexpression of human epidermal growth factor receptor 2 (HER2) is reported in breast [1,2], gastric [3], pancreatic [4], lung [5], and colorectal cancers [6]
H2Mab‐19 reacted with LN229/Human epidermal growth factor receptor 2 (HER2) and weakly reacted with LN229 cells (Fig. 1A), indicating that H2Mab‐19 is specific to HER2
The first objective of this study was the development of an anti‐HER2 monoclonal antibodies (mAbs) in either IgG2a or IgG2b subclasses using CasMab technology

Summary

Introduction

The overexpression of human epidermal growth factor receptor 2 (HER2) is reported in breast [1,2], gastric [3], pancreatic [4], lung [5], and colorectal cancers [6]. This expression is associated with poor clinical outcomes in patients with HER2‐positive breast cancer [1,2]. Even in low‐HER2‐expressing tumors, DS‐8201 shows antitumor activity This drug has several innovative features: i) a highly potent, novel payload with a high drug‐to‐antibody ratio, ii) good homogeneity, iii) a tumor‐selective cleavable linker, iv) a stable linker‐payload in circulation, and v) a cytotoxic agent with a short in vivo half‐life in vivo [13]. The cytotoxic payload can exert a bystander effect [13]

Objectives

Methods

Results

Conclusion