Researchers at the University of California, Los Angeles (UCLA) Health Sciences have developed a type of bispecific antibody that can activate the body’s T cells to kill cells infected with cytomegalovirus (CMV).
CMV is a common virus found worldwide and in people of all ages. In healthy individuals, it causes no or only mild symptoms. However, in people with suppressed or weakened immune systems, such as people with HIV, organ-transplant recipients, or infants, CMV can cause severe symptoms, which can even become life-threatening.
In babies, for instance, a CMV infection can cause deafness when the virus is transmitted from the mother to the fetus during pregnancy.
Once a person has been infected with CMV, they have it for life, with most CMV infections staying dormant in people with healthy immune systems. When the immune system becomes weakened, the CMV infection can flare up and cause dangerous symptoms.
Currently, individuals with a severe CMV infection are prescribed antivirals, but these can damage the bone marrow and kidneys, and can come with other severe side effects. Moreover, CMV can develop resistance to these drugs, rendering them futile.
For this reason, the UCLA researchers wanted to produce antibodies that could direct a patient’s own T cells to attack and kill cells that are already infected with CMV. In their recent study, published in the journal Science Advances and titled “Bi-Specific Antibodies Crosslink and Redirect CD8+ T Cells to Kill Cytomegalovirus-Infected Cells,” the researchers therefore engineered a type of antibody called a T cell-redirecting bispecific antibody (TRBA).
As a relatively new type of antibody, TRBAs have mainly been used to treat cancer. The TRBAs designed by the UCLA research team, however, work slightly differently.
The researchers designed three types of CMV-targeting TRBAs using the parental monoclonal antibody against CD3-epsilon, a transmembrane protein found on cytotoxic T cells, and the parental monoclonal antibody against glycoprotein H, which is found on the human CMV.
By combining these two parental monoclonal antibodies, the research team designed three TRBAs with a CD3-binding region and a glycoprotein H-binding region. These newly designed TRBAs can therefore act as a bridge between the cytotoxic T cells and the glycoprotein H found on the CMV-infected cells. As a result, the cytotoxic T cells are recruited by the TRBAs and cluster around the infected cells, attacking and killing them.
“The findings could pave an alternative way for treating infection without the current drugs, which are both expensive and often carry severe side effects,” said the leader of the study, Otto Yang, PhD, professor of medicine in the division of infectious diseases and of microbiology, immunology, and molecular genetics at the David Geffen School of Medicine at UCLA.
“This is a potentially new way to harness the immune system against this virus and could offer new opportunities to treat transplant patients or AIDS patients with life-threatening infection, or children with poorly controlled infection that puts them at risk for deafness.”
Yang added: “Hopefully, if there is commercial interest, these antibodies could be tested in clinical trials.”
