Cluster of Differentiation 276 (CD276) or B7 Homolog 3 (B7-H3) is a human
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
encoded by the
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
Structure
B7-H3 is a 316 amino acid-long
type I transmembrane protein
A single-pass membrane protein also known as single-spanning protein or bitopic protein is a transmembrane protein that spans the lipid bilayer only once. These proteins may constitute up to 50% of all transmembrane proteins, depending on the or ...
, existing in two
isoforms
A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene and are the result of genetic differences. While many perform the same or similar biological roles, some isoforms have uniqu ...
determined by its extracellular domain. In mice, the extracellular domain consists of a single pair of
immunoglobulin variable (IgV)-like and immunoglobulin constant (IgC)-like domains, whereas in humans it consists of one pair (2Ig-B7-H3) or two identical pairs (4Ig-B7-H3) due to
exon duplication. B7-H3
mRNA
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein.
mRNA is ...
is expressed in most normal tissues. In contrast, B7-H3 protein has a very limited expression on normal tissues because of its
post-transcriptional regulation
Post-transcriptional regulation is the control of gene expression at the RNA level. It occurs once the RNA polymerase has been attached to the gene's promoter and is synthesizing the nucleotide sequence. Therefore, as the name indicates, it occur ...
by
microRNAs. However, B7-H3 protein is expressed at high frequency on many different cancer types (60% of all cancers).
The 4Ig-B7-H3 isoform is predominant in cancer.
Function
In non-malignant tissues, B7-H3 has a predominantly inhibitory role in
adaptive immunity
The adaptive immune system (AIS), also known as the acquired immune system, or specific immune system is a subsystem of the immune system that is composed of specialized cells, organs, and processes that eliminate pathogens specifically. The ac ...
, suppressing
T cell activation and proliferation.
In malignant tissues, B7-H3 is an
immune checkpoint
Immune checkpoints are regulators of the immune system. These pathways are crucial for self-tolerance, which prevents the immune system from attacking cells indiscriminately. However, some cancers can protect themselves from attack by stimulat ...
molecule that inhibits tumor antigen-specific immune responses. B7-H3 also possesses non-immunological pro-tumorigenic functions such as promoting migration, invasion,
angiogenesis
Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis. Angiogenesis continues the growth of the vasculature mainly by processes of sprouting and ...
, chemoresistance,
epithelial-to-mesenchymal transition, and affecting tumor cell metabolism.
As a possible drug target
Due to its selective expression on solid tumors, B7-H3 has been the target of several anticancer agents such as
enoblituzumab (MGA271),
, MGD009, MGC018, DS-7300a, and
CAR T cells.
targeting the IgV and IgC domains of B7-H3 have been developed in the laboratory of Mitchell Ho at the
NCI,
NIH (Bethesda, US). The nanobody-based
CAR T cells are active in preclinical models of
pancreatic cancer
Pancreatic cancer arises when cell (biology), cells in the pancreas, a glandular organ behind the stomach, begin to multiply out of control and form a Neoplasm, mass. These cancerous cells have the malignant, ability to invade other parts of ...
and
neuroblastoma and show efficacy against large tumors in mice.
See also
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Cluster of differentiation
The cluster of differentiation (also known as cluster of designation or classification determinant and often abbreviated as CD) is a protocol used for the identification and investigation of cell surface molecules providing targets for immunophe ...
References
Further reading
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External links
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Clusters of differentiation
Single-pass transmembrane proteins
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