Two Strategies Give Virus-Specific Immunotherapy a Boost

Pediatric oncologist Michael Grimley, MD, talks about a novel immunotherapy at Cincinnati Children’s that uses virus-specific T cells (VSTs) for hematopoietic stem cell transplant (HSCT) recipients, and ways to make this therapy more broadly available.

Which patients may benefit from VST therapy?

Any immunocompromised patient can benefit, but our work focused initially on pediatric patients receiving a hematopoietic stem cell transplant (HSCT). Despite advances in HSCT therapy and supportive care, about half of these patients develop a viral infection after transplant. Antiviral agents may be effective, but there are significant side effects limiting their use.

What did this effort involve?

Some years ago, researchers at Baylor University and Texas Children’s Hospital developed a technique for manufacturing VSTs using donor-derived blood samples. They allowed us to cross-reference their work, and with their assistance, in 2014 we opened our protocol at Cincinnati Children’s to test the safety and efficacy of this therapy. The therapy can target the four most common viruses that occur after an HSCT—adenovirus (ADV), BK virus, cytomegalovirus (CMV) and Epstein-Barr virus (EBV).

This was exciting, but the available technology was slow—it could take four months to manufacture VST products. In 2017, we transitioned to a manufacturing system using peptide mix technology that allows us to manufacture the VSTs in 28 days, which has allowed us to make VSTs for virtually all of our HSCT patients at risk for viral complications.

Since 2014, 36 patients have received at least one infusion of VSTs through this protocol. On average, about 80% experienced a clinical benefit from the therapy, and we have seen no associated toxicity or graft vs. host disease.

What are the limitations of this therapy?

The manufactured product can only fight viruses to which the VST donor has already been exposed. Also, not everyone is willing to donate blood for virus-specific immunotherapy, which leaves some high-risk patients without an available cellular product. And if a donor does not develop a need for virus-specific therapy, the product goes to waste.

Our team decided to create a protocol using “off the shelf” VST therapy, targeting the same viruses. All of the VSTs are characterized for viral specificity and human leukocyte antigen (HLA) restriction. Any institution can send a patient’s HLA typing to us to see if we have a good match. The protocol is open to patients age 0 to 70 who can come to Cincinnati Children’s for the infusion. We have now treated 15 patients with these third-party VST products. So far, about two-thirds of those who have participated in this protocol experienced clinical benefit. Results from this protocol were presented at BMT Tandem meetings in March 2018.

What’s next?

In 2019, we are planning to open a trial that will study the prophylactic use of VST therapy for patients receiving a hematopoietic stem cell transplant. We also would like to investigate the role of VST therapy for other types of immunocompromised patients, such as those with post-transplant lymphoproliferative disease from solid organ transplants.

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