Custom Anti-TNFR-SF Agonistic Antibody Development Service

Tumor treatment can be achieved by artificially stimulating anti-tumor T lymphocytes and NK lymphocytes with agonist monoclonal antibodies. Creative Biolabs is doing this to help researchers succeed in tumor therapy by providing customized development of anti-tumor necrosis factor-receptor superfamily (TNFR-SF) agonist antibodies against members of the TNFR family expressed by T cells and NK cells.

Introduction of Anti-TNFR-SF Agonistic Antibody

TNFR-SF provides critical communication signals between various cell types during development, especially in the skin, bone and lymphatic organs, to maintain organ homeostasis and initiate tissue response. Several members of the TNFR-SF family can be expressed by T cells and NK cells, which especially transmit costimulatory signals on their surfaces. The cytosolic signal domain subdivides TNFR-SF into those receptors that use the death domain or bind to the TNF receptor-associated factor (TRAF) family of ubiquitin E3 ligase, or lack the cytosolic domain and function as decoy receptor. According to the specific cell environment, the outcome of TNFR signal may be cellular life, death or differentiation. The factors of this family are very important in the immune checkpoint pathway of tumors. By blocking the communication signal of TNFR-SF, they can enhance the immune activity of the body to tumors. Activating antibodies are an important means of activating TNFR-SF receptors, so the development of anti-TNFR-SF agonizing antibodies is very important in cancer therapy.

Fig.1 Intercellular networks formed by the cosignaling TNFR-SF. (Ward-Kavanagh, 2016)

Anti-TNFR-SF Agonistic Antibody in Tumor Therapy

In recent years, preclinical and clinical studies of antibodies specific for CD40-, CD27-, 4-1BB, and TRAILR2/DR5 have shown that binding to Fcγ receptors (FcγRs) is a critical step in releasing strong agonistic activity. The resulting activation of FcyR can counteract or even negate the intended effect of anti-TNF receptor antibodies, for example, disrupting targeted cells to trigger immunostimulatory tumor necrosis factor receptors. This finding made it possible to artificially stimulate anti-TNFR agonist monoclonal antibodies (mAbs) to achieve tumor therapy. Rich theoretical knowledge combined with our advanced antibody engineering platform, Creative Biolabs can provide agonist antibody development and customization services for the corresponding targets of the TNFR-SF family. These antibodies include, but are not limited to:

CD137 (4-1BB)	CD134 (OX40)
GITR (CD357)	CD40
CD27	CD30
CD28	DR5
BTLA	ICOS

To see the detailed introduction of family members, click here.

Among them, CD137-specific agonist mAbs have shown objective clinical activity in patients with metastatic melanoma, while anti-OX40 and anti-GITR-mAbs have entered clinical trials. Studies have shown that mAb therapy in contact with TNFR-SF members is more effective than traditional cancer therapy and additional immunotherapy. In fact, tumor antigen T cell responses caused by immunogenic tumor cell death are amplified by immunostimulatory agonist mAbs. In addition, anti-CD137 mAbs have been shown to enhance NK-mediated cytotoxicity induced by rituximab and trastuzumab. In combination with other immunomodulatory mAbs, blocking T cell checkpoint blocking receptors, such as CTLA-4 and PD-1, is also promising.

Fig.2 Schematic representation of the sites and cells on which agonist anti-CD137 mAbs act as an example of TNFR mAb mechanism. (Melero, 2013)

Anti-TNFR-SF Agonistic Antibody Development Services in Creative Biolabs

Creative Biolabs has accumulated valuable experience in the discovery of new agonist antibodies. Using phage display technology, we are confident to provide a fast and effective anti-TNFR-SF agonistic antibody discovery service. And provide one-stop integrated services in subsequent customized development. Our service features are:

High capacity and affinity of libraries, providing prefabricated library screening services
Various Fc engineering approaches can guide the design of engineered antibodies
Customized biological planning strategy
Total quality control verification
Good after-sales and competitive prices

If you are interested in our services, please feel free to contact us.

References

Ward-Kavanagh, L.K.; et al. The TNF receptor superfamily in co-stimulating and co-inhibitory responses. Immunity. 2016, 44(5): 1005-1019.
Melero, I.; et al. Agonist antibodies to TNFR molecules that costimulate T and NK cells. Clin Cancer Res. 2013, 19(5): 1044-1053.

All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.

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