Anti-B7-H6 Antibody Development

B7-H6, a member of the B7 family of immunoreceptors, is a cell-surface ligand for the NKp30-activating receptor expressed on natural killer (NK) cells. B7-H6 is not detected in normal human tissues at steady state but is expressed on tumor cells. Nowadays, Creative Biolabs is capable of offering a comprehensive set of antibody-related services from design to manufacturing. Remarkably, scientists at Creative Biolabs now provide customized antibody development services for either membrane-distal domain or membrane-proximal domain of B7-H6 with our advanced technique platforms.

B7-H6 Ectodomain Shedding

In humans, the activating natural cytotoxicity receptor NKp30 plays a vital role in NK cell-mediated tumor cell lysis. NKp30 recognizes the cell-surface protein B7-H6 which is expressed on different tumor cell lines but not healthy cells. The interaction of NKp30 on NK cells with B7-H6 on tumor cells leads to efficient NK-cell activation and target cell killing. B7-H6 is a 454 amino acid (aa) long type I transmembrane protein with a predicted molecular weight (MW) of 51 KDa. The extracellular domain of B7-H6 comprises two immunoglobulin-like domains and harbors several potential N-glycosylation sites.

Fig.1 Views of the NKp30–B7-H6 complex. (Li, 2011)

A disintegrin and metalloproteases (ADAM)-10 and ADAM-17 are involved in the ectodomain shedding of B7-H6, leading to decreased surface levels of B7-H6 on tumor cells and reduced NKp30-mediated recognition by NK cells. The soluble form of B7-H6 (sB7-H6) ligand downmodulates the expression of NKp30 on peritoneal/ascitic fluid (PF-NK) cells and also results in defective function of NKp30.

Fig.2 Substrates of ADAM17 in the tumor microenvironment. Substrates of ADAM17 are indicated in colored, molecules not shed by ADAM17 are in grey. (Lowe, 2016)

Antibody Strategies against B7-H6

Although shedding of B7-H6 could be inhibited by the matrix metalloproteases (MMP) and ADAM protease inhibitor in vitro, several inhibitors of ADAM17 have failed during clinical trials because of side effects and lack of efficacy. The difference between in vitro and in vivo may be due in part to pharmacokinetic factors coming into play when considering the whole organism and an incomplete understanding of the biology of ADAM17 inhibition. This is not unique for ADAM17 inhibitors but rather a universal problem in the development of therapeutic enzyme inhibitor.

Although the site of proteolytic shedding remains to be unclear, antibodies could also be exploited to improve the current situation. The membrane-distal domain of sB7-H6 could be regarded as targets to develop antibodies to neutralize itself, thereby preventing any possible soluble component-induced activities beneficial to tumor development. Antibodies targeted the membrane-proximal domain of B7-H6 can be conjugated with a drug to kill cancer cells. Here, antibodies are only responsible for taking drugs to the tumor cells surroundings instead of neutralizing sB7-H6.

Features

• Quality backed by experienced technical and customer support teams, as well as state-of-the-art facilities.
• Specialized in antibody customization service with the completion of numerous antibody-related projects.
• Fast turnaround time and competitive pricing .

With Ph.D. level scientists and rich experience in recombinant antibody production, antibody engineering, and bio-conjugation, Creative Biolabs is dedicated to providing customized services against B7-H6 to meet your R&D timeline and budget. Please contact us for more information and a detailed quote.

References

1. Li, Y.; et al. Structure of the human activating natural cytotoxicity receptor NKp30 bound to its tumor cell ligand B7-H6. Journal of Experimental Medicine. 2011, 208(4), 703-714.
2. Lowe, P. R.; Corvaia, N. ADAM17: a gatekeeper in immune-oncology. Int J Cancer Clin Res. 2016, 3, 058.

For Research Use Only. NOT FOR CLINICAL USE.