New Trial Tests Cell Therapy for Neonates With CMV 

A first-of-its-kind clinical trial at Children’s Hospital Los Angeles is investigating a novel protocol for neonates with congenital cytomegalovirus (CMV): virus-specific T-cell therapy.

The phase 2 randomized trial represents a potentially groundbreaking approach to treating congenital CMV in newborns—which can lead to hearing loss and deafness, developmental delays, vision loss, and more. Antiviral medication is the current standard of care, but it can cause serious side effects.

CHLA is one of just four centers in the country—and the only one on the West Coast—to offer this new trial.

“Congenital CMV can have devastating impacts that can affect a child’s entire life,” says Philippe Friedlich, MD, MSEpi, MBA, Chief of Neonatology and Co-Director of the Fetal and Neonatal Institute at Children’s Hospital Los Angeles. “The hope is that cell therapy can offer a safer and more effective treatment option for these babies.”

Harnessing a mother’s immunity

CMV is a common virus that doesn’t cause symptoms in most people with healthy immune systems. But approximately 1 in 200 babies acquire the infection in the womb—and 20% of those newborns will have birth defects or long-term health problems.

The clinical trial plans to enroll 30 neonates who are less than 1 month of age and have moderate to severe congenital CMV. Babies will be randomized into two groups: One will receive standard antiviral therapy with valganciclovir or ganciclovir, and one will receive both antiviral therapy and CMV-specific T-cells.

Those CMV-specific T-cells will come from a donor who is half-matched with the patient: the baby’s mother.

“If a baby has congenital CMV, then obviously the mother will be infected because transmission was in utero,” says Neena Kapoor, MD, Director of the Transplant and Cell Therapy Laboratory at Children’s Hospital Los Angeles. “The goal is to harness the mother’s immunity and give it to the baby.”

At CHLA, the trial is a collaboration between the Cancer and Blood Disease Institute and the Fetal and Neonatal Institute. Dr. Kapoor currently participates in similar studies testing virus-specific T-cells in children undergoing bone marrow transplant who contract CMV.

“It’s still experimental, but we have had success with this approach in transplant patients,” she says. “We want to see if it will be an effective treatment for neonates with congenital CMV.”

A tiny dose of cells

Under the protocol, mothers will first be screened to confirm that they have T-cells that produce gamma interferon in response to CMV.

If the mother is a good candidate, the team collects a larger sample of her blood cells and takes them to the Transplant and Cell Therapy Laboratory at CHLA. There, the T-cells that produce gamma interferon against CMV are electromagnetically separated out from the rest of the blood. A special machine processes the cells in just two days.

The baby is then given a tiny dose of these CMV-specific T-cells via an intravenous infusion. An additional dose is given once every two weeks until the infection has cleared. No more than five infusions will be given.

“The idea is that those T-cells, which are already educated to recognize and kill CMV, will then proliferate in the baby’s body and fight the infection,” Dr. Kapoor says.

Although the mother is only a half-match for the child, giving just a tiny dose of the interferon-producing cells should minimize risk of the baby developing graft-versus-host disease, she adds. Babies are also monitored closely for any signs of cytokine release syndrome.

“We have not seen cytokine release syndrome in transplant patients who receive CMV-specific T-cells,” Dr. Kapoor notes. “But it is a potential risk, so we monitor babies very carefully.”

Early diagnosis is key

Dr. Friedlich notes that it’s important that physicians identify CMV in neonates as early as possible—before potentially irreversible damage occurs. Signs to look for include:

• Enlarged spleen or liver
• Elevated liver enzymes
• Microcephaly (small head)
• Hearing loss

Only patients younger than 28 days can participate in the trial. “The hope is that cell therapy will be able to control the infection early on, so we can minimize hearing loss and neurodevelopmental impacts,” he says.

He adds that this trial could open the door to more advanced personalized medicine applications for critically ill neonates.

“In neonatology we have not had much integration with personalized medicine and cell therapy,” Dr. Friedlich adds. “I see this as the next frontier in our field and an opportunity to make a real difference in patients’ lives.”