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Analyzing Tumor and Tissue Distribution of Target Antigen Specific Therapeutic Antibody
Published on: May 16, 2020
Novel humanized monoclonal antibodies against ROR1 for cancer therapy
Rong Wei1, Xun Liao1, Jiao Li1
1Laboratory of Molecular Oncology, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China.
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.
Insights
Two novel humanized monoclonal antibodies targeting receptor tyrosine kinase-like orphan receptor 1 (ROR1) demonstrated significant anti-tumor effects. These antibodies effectively suppressed cancer cell proliferation and migration in preclinical models.
Area of Science:
- Oncology
- Immunology
- Biotechnology
Background:
- Overexpression of receptor tyrosine kinase-like orphan receptor 1 (ROR1) is linked to cancer progression, including proliferation, survival, and migration.
- ROR1 is recognized as a promising therapeutic target for various cancers.
- This research focuses on developing and evaluating novel ROR1-targeting monoclonal antibodies.
Purpose of the Study:
- To develop humanized monoclonal antibodies against ROR1.
- To investigate the anti-tumor efficacy of these novel antibodies.
Main Methods:
- ROR1 expression was assessed in tumor tissues and cell lines using immunohistochemistry and flow cytometry.
- Mouse hybridoma antibodies were humanized via complementarity-determining region (CDR) grafting.
- Antibody characterization involved surface plasmon resonance, ELISA, and flow cytometry, with anti-tumor activity evaluated through in vitro and in vivo assays.
Main Results:
- ROR1 was significantly overexpressed in lung adenocarcinoma, liver cancer, and breast cancer.
- Two humanized ROR1 monoclonal antibodies, h1B8 and h6D4, were successfully developed with high specificity and affinity.
- These antibodies demonstrated potent suppression of tumor growth in lung, liver, and breast cancer mouse models.
Conclusions:
- Two humanized monoclonal antibodies, h1B8 and h6D4, targeting ROR1 were successfully generated.
- These antibodies exhibited significant in vivo anti-tumor activity, validating ROR1 as a therapeutic target.
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