Journal Article

Novel humanized monoclonal antibodies against ROR1 for cancer therapy

Wei, Rong, Peng, Yong, Liao, Xun, Li, Jiao, Ming, Yue, Mu, Xiaoyu

2024

Overview

Background Overexpression of receptor tyrosine kinase-like orphan receptor 1 (ROR1) contributes to cancer cell proliferation, survival and migration, playing crucial roles in tumor development. ROR1 has been proposed as a potential therapeutic target for cancer treatment. This study aimed to develop novel humanized ROR1 monoclonal antibodies and investigate their anti-tumor effects. Methods ROR1 expression in tumor tissues and cell lines was analyzed by immunohistochemistry and flow cytometry. Antibodies from mouse hybridomas were humanized by the complementarity-determining region (CDR) grafting technique. Surface plasmon resonance spectroscopy, ELISA assay and flow cytometry were employed to characterize humanized antibodies. In vitro cellular assay and in vivo mouse experiment were conducted to comprehensively evaluate anti-tumor activity of these antibodies. Results ROR1 exhibited dramatically higher expression in lung adenocarcinoma, liver cancer and breast cancer, and targeting ROR1 by short-hairpin RNAs significantly inhibited proliferation and migration of cancer cells. Two humanized ROR1 monoclonal antibodies were successfully developed, named h1B8 and h6D4, with high specificity and affinity to ROR1 protein. Moreover, these two antibodies effectively suppressed tumor growth in the lung cancer xenograft mouse model, c-Myc/Alb-cre liver cancer transgenic mouse model and MMTV-PyMT breast cancer mouse model. Conclusions Two humanized monoclonal antibodies targeting ROR1, h1B8 and h6D4, were successfully developed and exhibited remarkable anti-tumor activity in vivo.

• Publisher: BioMed Central,BioMed Central Ltd,BMC
• Subject: Affinity / Animal experimentation / Animals / Antibodies, Monoclonal, Humanized - immunology / Antibodies, Monoclonal, Humanized - therapeutic use / B cells / Biomedical and Life Sciences / Biomedicine / Cancer / Cancer Research / Care and treatment / Cell Line, Tumor / Cell Movement / Cell Proliferation / Development and progression / Disease Progression / Enzyme-linked immunosorbent assay / Genetic engineering / Health aspects / Humanized antibody / Humans / Immunotherapy / Liver cancer / Lung cancer / Mice, Inbred BALB C / Mice, Nude / Monoclonal antibodies / Neoplasms - immunology / Neoplasms - pathology / Neoplasms - therapy / Oncology / Receptor Tyrosine Kinase-like Orphan Receptors - immunology / ROR1 / Specificity / Tyrosine / Xenograft Model Antitumor Assays