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BsAb Application in Hematology

Being world-famous for its superior bispecific antibody (BsAb) products and services, Creative Biolabs offers custom services to produce different types of BsAbs for the treatment of blood diseases. With professional scientists here, we are confident in providing first class BsAbs to meet your project development.

Hematology concerns about blood diseases that affect the production of blood components or cause problems in blood coagulation. Blood cancers (e.g., leukemia, myeloma, and lymphoma), bleeding disorders (e.g., hemophilia), and blood clots are some examples of such diseases. Research on hematology is often closely related to oncology study and many times shares similar therapeutic strategies. Efforts have been made to apply BsAbs to the application of hematology, including treatment of different kinds of blood cancers such as acute myeloid leukemia (AML), B cell acute lymphoblastic leukemia (B cell ALL), chronic lymphocytic leukemia (CLL), and hemophilia.

For current BsAb drugs developed for blood disease treatment, there are two major mechanisms, T cell recruitment and forced protein association.

T Cell Recruitment

BsAb can bind to CD3 on T cells and tumor-associated antigens on tumor cells at the same time. In this way T cells are redirected to tumor cells, activated, and then release T cell cytokines such as TNF-α and IFN-γ. Eventually, tumor cells are lysed. This strategy has been applied to hematology. Blinatumomab is a BiTE BsAb for B cell acute ALL, non-Hodgkin lymphoma (NHL), and diffuse large B cell lymphoma (DLBCL). It binds CD3 on T cells and CD19 on CD19-expressing B cell malignancies, and is the first BsAb approved by the FDA. FBTA05 is a Triomab from Technische Universität München, designed for patients with CD20-positive B cell malignancies. MGD006 (from MacroGenics) is a DART BsAb that specifically redirects T cells to leukemic cells in AML.

Quantitative analysis of the released BsAb CD33-CD3 by cryogel-housed MSCs. Part A shows the cryogel-housed scBsAb-releasing MSCs system, and Part B shows the amount of BsAb CD33-CD3 produced by modified MSCs seeded at reported seeding densities in the cryogel scaffold. (Aliperta, R., 2017)

Figure 1. Quantitative analysis of the released BsAb CD33-CD3 by cryogel-housed MSCs. Part A shows the cryogel-housed scBsAb-releasing MSCs system, and Part B shows the amount of BsAb CD33-CD3 produced by modified MSCs seeded at reported seeding densities in the cryogel scaffold. (Aliperta, R., 2017)

Forced Protein Association

BsAbs are capable of binding two ligands/ antigens at the same time, and trigger subsequent reactions in certain signaling pathways. Factor VIII (FVIII), also known as anti-hemophilic factor (AHF), is an essential blood-clotting protein that circulates in the bloodstream. Upon injury, the active form of the protein (Coagulation factor VIIIa) interacts with Factor IXa and Factor X in the coagulation cascade. This interaction activates Factor X and triggers a chain of reactions that form a blood clot. However, in patients with the bleeding disorder hemophilia A, coagulation factor VIIIa is missing. RG6013 is a KIH BsAb designed to bring together Factor IXa and Factor X. It mimics the coagulation factor VIIIa in health people and triggers subsequent pathways. Its Fc region ensures a long serum half-life of the drug.

The integrated antibody engineering and production platforms and the unbeatable research team in Creative Biolabs guarantee satisfying, time-saving and budget-saving BsAb services for our customers. We are always ready to assist your research in science and medicine.

References

1. Aliperta, R.; et al. Cryogel-supported stem cell factory for customized sustained release of bispecific antibodies for cancer immunotherapy. Scientific Reports. 2017, 7: 42855.
2. Weiner, L. M.; et al. Antibody-based immunotherapy of cancer. Cell. 2012, 148(6): 1081-1084.

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