Preprint

Article

Antitumor Activities by a Humanized Cancer-Specific anti-HER2 Monoclonal Antibody (humH₂Mab-250) in Xenograft Models of Human Breast Cancer

Altmetrics

Downloads

Views

Comments

Supplementary Material

supplementary.pdf (642.49KB )

This version is not peer-reviewed

Submitted:

12 November 2024

Posted:

13 November 2024

You are already at the latest version

Alerts

Abstract

Monoclonal antibody (mAb) and cell-based immunotherapies represent cutting-edge strategies for cancer treatment. However, safety concerns persist due to the potential targeting of normal cells that express reactive antigens. Therefore, it is crucial to develop cancer-specific mAbs (CasMabs) that can bind to cancer-specific antigens and exhibit antitumor activity in vivo, thereby reducing the risk of adverse effects. We previously screened mAbs targeting human epidermal growth factor receptor 2 (HER2) and successfully developed a cancer-specific anti-HER2 mAb, H₂Mab-250/H₂CasMab-2 (mouse IgG₁, kappa). In this study, we assessed both the in vitro and in vivo antitumor efficacy of the humanized H₂Mab-250 (humH₂Mab-250). Although humH₂Mab-250 showed lower reactivity to HER2-overexpressed Chinese hamster ovary-K1 (CHO/HER2) and breast cancer cell lines (BT-474 and SK-BR-3) than trastuzumab in flow cytometry, both humH₂Mab-250 and trastuzumab showed similar antibody-dependent cellular cytotoxicity (ADCC) against CHO/HER2 and the breast cancer cell lines in the presence of effector splenocytes. In addition, humH₂Mab-250 exhibited significant complement-dependent cellular cytotoxicity (CDC) in CHO/HER2 cells compared to trastuzumab. Furthermore, humH₂Mab-250 possesses compatible in vivo antitumor effects against breast cancer xenografts with trastuzumab. These findings highlight the distinct roles of ADCC and CDC in the antitumor effects of humH₂Mab-250 and trastuzumab and suggest a potential direction for the clinical development of humH₂Mab-250 for HER2-positive tumors.

Keywords:

Subject: Medicine and Pharmacology - Oncology and Oncogenics

Copyright: This open access article is published under a Creative Commons CC BY 4.0 license, which permit the free download, distribution, and reuse, provided that the author and preprint are cited in any reuse.