B7-H4, also known as B7S1, B7x, and VTCN1, is a member of the B7 family of immune modulators. B7-H4 is a transmembrane protein that binds an unknown receptor on activated T cells resulting in inhibition of T-cell effector function via cell cycle arrest, reduced IL-2 production, and decreased proliferation. The B7-H4 protein possesses 282 amino acid residues containing an amino-terminal extracellular domain, a large hydrophobic transmembrane domain, and a very short intracellular domain with only two amino acids. B7-H4 possesses a pair of Ig-like regions and seven potential N-glycosylation sites in its extracellular domain.
In healthy individuals, B7-H4 mRNA is detected at low levels in many non-lymphoid tissues. However, B7-H4 protein expression seems to be limited due to tight translational control in peripheral tissues in humans. B7-H4 is up-regulated on the surface of cancer cells and immunosuppressive tumor-associated macrophages in a variety of human cancers. The expression of B7-H4 is up-regulated by IL10 and IL6 and is inhibited by IL4 and GM-CSF on antigen-presenting cells (APCs).
Besides being present on the cell surface, B7-H4 can also be cleaved from the surface of cells via the metalloproteinase nardilysin (NRD1). Levels of soluble serum B7-H4 (sB7-H4) correlate with tumor stage, poor prognosis, and pathological types. sB7-H4 is highly expressed in inflammation, tumors, autoimmune diseases, and pregnancy. Measurement of sB7-H4 levels may provide helpful information for the unique diagnosis of different types of hematological malignancies.
Studies have shown that B7-H4 is involved in mitochondrial signal transduction, IL6/JAK/STAT3 signal pathway, IL6/JAK/STAT3 signal pathway, and CXCL12/CXCR4 signal pathway. Key elements in these signaling pathways could serve as research points for the development of therapeutic strategies.
B7-H4 plays a role in immune evasion and tumorigenesis; eliminating or diminishing the effects of B7-H4 may positively affect the host immune response and negatively affect tumor cell survival simultaneously. Potential methods targeting B7-H4 include siRNA, immunotoxins, blocking antibodies, T-cell-based immunotherapy, antibody-drug conjugate (ADC), and vaccine. For instance, locking the putative B7-H4 receptor on T cells from engaging with B7-H4 on the surface of tumor cells or macrophages could be achieved using an anti-B7-H4 antibody. An anti-B7-H4-specific CAR could be generated by combining an anti-B7-H4 single-chain variable fragment (scFv) with optimal T cell co-stimulation domains.
Creative Biolabs is competent to provide B7-H4-based immunotherapy agents, including mAbs, ADC, bispecific antibody, and CAR-T cells, with acceptable efficacy. A comprehensive set of immune checkpoint molecule research services are available for you to support your project. For any questions, please do not hesitate to contact us for more information.
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