ArticleThe Journal of biological chemistry2020
Affinity maturation, humanization, and co-crystallization of a rabbit anti-human ROR2 monoclonal antibody for therapeutic applications.
Article in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 34 citations in OpenAlex.
- The multifaceted roles of receptor tyrosine pseudokinases in cellular signalling.Biochemical Society transactions · 2026Review
- ROR2-specific CAR T cells are effective against hematologic and solid tumors and well tolerated in mice.Cell reports. Medicine · 2025Article
- ROR2 Regulates Cellular Plasticity in Pancreatic Neoplasia and Adenocarcinoma.Cancer discovery · 2024Article
- Structure and function of the ROR2 cysteine-rich domain in vertebrate noncanonical WNT5A signaling.eLife · 2024Article
- A chemical proteomics approach for global mapping of functional lysines on cell surface of living cell.Nature communications · 2024Article
- ROR2 regulates cellular plasticity in pancreatic neoplasia and adenocarcinoma.bioRxiv : the preprint server for biology · 2024Article
- A mammalian cell display platform based on scFab transposition.Antibody therapeutics · 2023Article
- Concerted Antibody and Antigen Discovery by Differential Whole-cell Phage Display Selections and Multi-omic Target Deconvolution.Journal of molecular biology · 2023Article
- A novel humanized Chi3l1 blocking antibody attenuates acetaminophen-induced liver injury in mice.Antibody therapeutics · 2023Article
- ROR1-targeting switchable CAR-T cells for cancer therapy.Oncogene · 2022Article
- Crystal structure of the kringle domain of human receptor tyrosine kinase-like orphan receptor 1 (hROR1).Acta crystallographica. Section F, Structural biology communications · 2022Article
- Retrospective analysis of the preparation and application of immunotherapy in cancer treatment (Review).International journal of oncology · 2022Article
- WNT11/ROR2 signaling is associated with tumor invasion and poor survival in breast cancer.Journal of experimental & clinical cancer research : CR · 2021Article
- ROR2 has a protective role in melanoma by inhibiting Akt activity, cell-cycle progression, and proliferation.Journal of biomedical science · 2021Article
- ROR and RYK extracellular region structures suggest that receptor tyrosine kinases have distinct WNT-recognition modes.Cell reports · 2021Article
- Prognostic Significance of ROR2 Expression in Patients with Urothelial Carcinoma.Biomedicines · 2021Article
- Antibody-based cancer therapy.Oncogene · 2021Review
- Effective rational humanization of a PASylated anti-galectin-3 Fab for the sensitive PET imaging of thyroid cancer in vivo.Scientific reports · 2021Article
- Adoptive T cell immunotherapy for medullary thyroid carcinoma targeting GDNF family receptor alpha 4.Molecular therapy oncolytics · 2021Article
- Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Antibodies are widely used as cancer therapeutics, but their current use is limited by the low number of antigens restricted to cancer cells. A receptor tyrosine kinase, receptor tyrosine kinase-like orphan receptor 2 (ROR2), is normally expressed only during embryogenesis and is tightly down-regulated in postnatal healthy tissues. However, it is up-regulated in a diverse set of hematologic and solid malignancies, thus ROR2 represents a candidate antigen for antibody-based cancer therapy. Here we describe the affinity maturation and humanization of a rabbit mAb that binds human and mouse ROR2 but not human ROR1 or other human cell-surface antigens. Co-crystallization of the parental rabbit mAb in complex with the human ROR2 kringle domain (hROR2-Kr) guided affinity maturation by heavy-chain complementarity-determining region 3 (HCDR3)-focused mutagenesis and selection. The affinity-matured rabbit mAb was then humanized by complementarity-determining region (CDR) grafting and framework fine tuning and again co-crystallized with hROR2-Kr. We show that the affinity-matured and humanized mAb retains strong affinity and specificity to ROR2 and, following conversion to a T cell-engaging bispecific antibody, has potent cytotoxicity toward ROR2-expressing cells. We anticipate that this humanized affinity-matured mAb will find application for antibody-based cancer therapy of ROR2-expressing neoplasms.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.