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Bispecific Antibody Application in Osteology

Creative Biolabs has been dedicated to the development of bispecific antibody (BsAb) therapeutics and is widely praised for its superior products and services. Based on our well established BsAb production platform, we provide high quality BsAb for osteology application.

Bone remodeling is a dynamic process which is a good balance between bone formation and resorption. This delicate balance maintains the bone integrity and the phosphocalcic homeostasis at different stages of life. However, tumors can develop in bones and disrupt bone remodeling. BsAbs are promising next generation therapeutics in various disciplines, including osteology.

Bone Tumor Related Factors

Functional crosstalk between osteoclasts (derived from hematopoietic stem cells and is involved in bone resorption) and osteoblasts (originated from bone marrow mesenchymal stem cells and specialized in bone apposition) is crucial for bone remodeling. Tumor originated from bone cell lineage or from nonosseous origins can both develop in bones. These tumors are caused by malfunctioning crosstalk between osteoclasts and osteoblasts. The early stage of tumor development features in the activation of osteoclast differentiation and recruitment of mature osteoclasts. This leads to matrix degradation of bone tissue and vast release of growth factors stored in it. These released soluble factors circulate around the body and then in return stimulate the proliferation and migration of tumor cells. The dysregulation of the balance between osteoclasts and osteoblasts results in osteoblastic, osteolytic, or osteoblastic–osteoclastic mixed lesions.

Schematic diagram of the RANK signaling pathways. The RANK receptor lacks intrinsic enzymatic activity and uses interaction with adaptor and docking proteins, such as TRAFs 2, 3, 5, and 6, Gab2, and Cbl to activate downstream signaling. (Walsh, M. C., 2014)

Figure 1. Schematic diagram of the RANK signaling pathways. The RANK receptor lacks intrinsic enzymatic activity and uses interaction with adaptor and docking proteins, such as TRAFs 2, 3, 5, and 6, Gab2, and Cbl to activate downstream signaling. (Walsh, M. C., 2014)

Since pathways in bone remodeling are very important for cancer development in bones, antigen/receptor signaling is pointed out as suitable drug targets. Research indicated that Receptor Activator of NFkB Ligand (RANKL) is an essential factor of osteoclastogenesis in vivo. RANKL can bind directly to RANK on RANK-expressing tumor cells, and then stimulate epithelial-mesenchymal transition and cell migration. RANKL can also activate bone resorption defining and osteoclast-dependent pathway, as well as osteoclastogenesis, all of which stimulate bone tumor development. Therefore RANKL has direct and indirect roles in bone tumor development.

Examples of BsAbs

Therapies have been developed to target RANKL itself and the RANKL/RNAK signaling pathway in order to treat these malignant diseases. ALX-0141 is a nanobody BsAb designed to treat bone loss related disorders (e.g., postmenopausal bone loss), and is currently in phase I clinical trials. It consists of two anti-RANKL nanobody units linked to an anti-HAS nanobody. The Phase I trial results are very promising as ALX 0141 is proved to be a potent RANKL inhibitor. ALX-0141 may be further developed for bone resorptive diseases, such as in cancer-related bone diseases, osteoporosis, and other disorders.

ALX-0141 binds to and inhibits RANKL.

Figure 2. ALX-0141 binds to and inhibits RANKL.

Creative Biolabs formulates appropriate strategies to develop BsAbs for specific scientific and/or clinical research purposes based on customers’ requests. Well experienced in BsAb design and production, Creative Biolabs is here to assist customers in designing BsAbs to block or activate signaling pathways involved in osteoclasts differentiation and activity.


1. Walsh, M. C.; Choi Y. Biology of the RANKL–RANK–OPG system in immunity, bone, and beyond.” Frontiers in immunology. 2014, 5: 511.
2. Schoen, P.; et al. Anti-RANKL Nanobody ALX-0141 shows sustained biomarker inhibition in a phase I study in healthy postmenopausal women. Bone Abstr. 2013,10: 1530.

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