Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a type I surface protein expressed during embryogenesis that contributes to polarized migration and organogenesis. Identification of membrane proteins expressed preferentially on tumor cells is a goal of drug development. This approach permits the design of vectorized compounds such as antibody drug conjugates (ADCs), and reduces undesirable side effects of therapeutic targeting of normal tissue. BOC Sciences has built a world-leading bioconjugation technology platform. We provide comprehensive ADC development services for ROR1-targeted cancer therapies. We have accumulated rich research data and practical project experience in the interaction of target and antibody, and provide customers with integrated ADC development services from R&D to GMP production.
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ROR1 is a transmembrane protein in the receptor tyrosine kinase (RTK) family. The ROR1 gene is highly expressed during early embryonic development and plays an important role in regulating embryonic muscle and bone development. However, during fetal development, ROR1 expression is turned off, so normal adult cells and tissues do not express this protein. In stark contrast to the negligible expression of ROR1 in normal adult tissues, significant expression of ROR1 was detected in several cancers, suggesting that this transmembrane protein can be considered a tumor-specific cell surface antigen.
Fig. 1. Examples of antibody-drug conjugates targeting ROR1 (Blood. 2021, 137(24): 3365-3377).
ROR1 is highly expressed in human tumors including breast, lung or ovarian cancer. The differential expression of ROR1 protein in various tumor cells makes it an interesting target for ADC design. Currently, ADC drugs targeting the ROR1 protein are in the early stages of clinical development, with most trials focusing on B-cell chronic lymphocytic leukemia, small lymphocytic lymphoma, and mantle cell lymphoma. For example, VLS-101 is an ADC drug composed of a humanized UC-961 antibody conjugated to monomethyl auristatin E (MMAE) through a cleavable linker, maintaining the high affinity and specific binding ability of UC-961. Currently, VLS-101 is undergoing Phase I-II studies as monotherapy and combination therapy in patients with hematological cancers and solid tumors.
Receptor tyrosine kinases are transmembrane proteins involved in the transmission of external signals through ligand binding. Phosphorylation of the kinase domain will lead to the activation of intracellular signaling cascades, leading to changes in cellular function. In recent years, several strategies have been developed aiming to exploit these receptors as drug development targets for ADCs, CAR-T cell therapy or antibody-conjugated nanoparticles. With a deep understanding of the ADC and oncology therapeutic areas, BOC Sciencesˈ scientists enable to offer the following ADC development services for ROR1-targeted therapies:
|Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer deaths worldwide. Aberrant overexpression of ROR1 in lung cancer cells further demonstrates that ROR1 kinase is a potential target for NSCLC therapy.
|Breast cancer is the most common cancer in women. Studies have shown that high-level expression of ROR1 mRNA is associated with high-grade tumors and metastasis, making it a promising therapeutic target for breast cancer.
|Ovarian cancer is one of the most common gynecological cancers with the highest mortality rate. The carcinoembryonic surface antigen ROR1 is expressed on human ovarian cancer stem cells (CSCs) and can be targeted for anti-CSC therapy.
|Pancreatic cancer is an aggressive malignancy, which is associated with high levels of metastasis. ROR1 may be considered a potential biomarker and therapeutic target for the treatment of pancreatic cancer.
|Mantle Cell Lymphoma
|Mantle cell lymphoma is a rare, aggressive and incurable subtype of non-Hodgkin’s B-cell lymphoma. Studies have found that ROR1 is expressed in most mantle cell lymphoma cells, which represents a tumor-specific therapeutic target.
|Chronic Lymphocytic Leukemia
|ROR1 is expressed on the surface of leukemia cells in chronic lymphocytic leukemia patients, but not on normal B cells or other tissues, making ROR1 an attractive candidate for targeted therapy.
|Diffuse Large B Cell Lymphoma
|Studies have shown that the receptor tyrosine kinase ROR1 is highly expressed on the cell surface of diffuse large B-cell lymphoma (DLBCL). Various preclinical and clinical stage evaluation studies are currently underway for ROR1-targeted therapy in patients with DLBCL tumors.
BOC Sciences' mission is to dramatically accelerate drug discovery by delivering a new class of ADC therapeutics. BOC Sciences works with companies and academic groups around the world, including most of the top biopharmaceutical companies, to help partners bring their ADC medicines to market by providing all preclinical activities and one-stop ADC solutions targeting different receptors. BOC Sciences is committed to expanding the scope of ADC development and manufacturing. Click here for more targeted ADC development services.