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BsAb Application in Oncology

Creative Biolabs is world-famous for its superior specific antibody (BsAb) products and services. Based on our well-established BsAb development platform, we offer custom services to produce different types of BsAbs to meet customers’ demands.

A bispecific monoclonal antibody (BsMAb, BsAb) is an artificial protein that is capable of binding two different antigens/proteins/receptors. The most well-known application of BsAb is cancer treatment, in which BsAbs are engineered to interfere with signaling pathways involved in tumor development, or redirect cytotoxic immune cells, such as T cells and NK cells to kill tumors, or deliver radioactive therapeutics to tumor cells.

Schematic diagram of the strategies for targeting tumour and tumour microenvironment.

Figure 1. Schematic diagram of the strategies for targeting tumour and tumour microenvironment. Part A shows the direct targeting of tumour cells; Part B shows the modulation of immune response; Part C shows the targeting tumour-associated M2-like macrophages; and Part D shows the targeting tumour-associated endothelial cells and stromal cells by BsAb. (Zhu, Y., 2015)

BsAbs for Immune Cell Recruitment

The essential immune system is very important for tumor prevention and treatment. In recent years, many therapies have been designed to utilize BsAbs to recruit immune cells of patients to treat different types of cancers. Most BsAbs in this category act through T cell recruitment and NK cell recruitment. They are designed to bind tumor-associated antigens (on tumor cells) and CD3 (on T cells) or CD16 (FcγRIII)/CD56 (on NK cells). BiTE, Triomab, DART, TandAb, and Tandem scFv-Fc BsAb are some popular BsAb formats designed for this purpose. At the same time, the Fc region-containing BsAbs also recognize Fcγ receptor (FcγR) and recruit accessory cells (e.g., dendritic cells, NK cells, and macrophages) to tumor cells. A combination of ADCC, phagocytosis, and T cell-mediated lysis is the cause of tumor cell killing. Some promising drugs (Blinatumomab, MGD007, Ertumaxomab, and FBTA05) have already been tested in clinical trials or approved for cancer treatment.

BsAbs for Signaling Pathway Interference

The development of cancer involves abnormal cell proliferation, cell motility, and angiogenic development. The ligand-receptor interactions in these pathways are targeted by BsAbs to stop the progression of cancers. BsAbs are capable of interfering with two (or more) receptors or ligands in these pathways simultaneously. They can block a signaling pathway and its backup pathway, or block one pathway at two points. (scFv)2-HSA BsAb MM111 and MM141, DAF-IgG RG7597, orthogonal BsAb LY3164530, CrossMab BsAb RG7221, and DVD-IgG BsAb ABT122 have been engineered to block receptor tyrosine kinases (RTKs), growth factors, metastasis factors, angiogenesis or vasculogenesis factors, and tumor necrosis factor (TNF). They showed promising test results and are in different stages of clinical trials.

BsAbs for Payload Delivery

The bispecificity of BsAb can also be applied to payload (drugs, radiolabels or other small molecules) delivery in oncology. Payload delivery mediated by BsAbs has higher sensitivity and specificity in imaging in radioimmunodetection and shows encouraging therapeutic effects in pretargeting radioimmunotherapy. A DNL BsAb TF2 is designed to bind a radiolabeled hapten-peptide and a CEA epitope on the surface of solid tumors. It allows targeted delivery of radioimmunotherapy. BsAb fragments have short half-lives (due to the lack of the Fc fragment), which ensure their rapid clearance from the body, low background noise, and low toxicity.

Creative Biolabs possesses integrated antibody engineering and production platforms. Our professional research team in Creative Biolabs is experienced in BsAb services for the application of oncology and is here to assist your research.

References

1. Zhu, Y.; et al. Multifunctional receptor-targeting antibodies for cancer therapy. The Lancet Oncology. 2015, 16(15): e543-e554.
2. Weiner, L. M.; et al. Antibody-based immunotherapy of cancer. Cell. 2012, 148(6): 1081-1084.

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