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Michael Keller

Virus-specific t-cells show promise before transplant in SCID patients

Michael Keller

“Today, we know that virus-specific T-cells can help protect patients from dangerous viruses after stem cell transplants,” says Michael Keller, M.D. “Through this research, we used the same therapy and approach, but applied it pre-transplant with the hope of providing the same benefit of protection against life-threatening viruses to patients who need it the most.”

Experts at Children’s National Health System have been successfully studying the use of virus-specific T-cells (VST) to help protect immunocompromised patients from life-threatening viruses after bone marrow transplants. Research published recently in the Biology of Blood and Marrow Transplantation presents promising new findings from testing the use of these same VSTs before transplant to help give patients with severe combined immunodeficiency (SCID) a better chance at long-term survival.

Babies born with SCID are highly susceptible to severe infections that are often fatal if not treated with immune-restoring treatments, like hematopoietic stem cell transplants (HSCT). However, undergoing an HSCT with an infection present has shown to lead to a decrease in survival at two years old for SCID patients when compared to those who start the HSCT infection-free. The study lead, Michael Keller, M.D., hypothesized that the success of HSCTs in SCID patients may be improved by controlling severe viral infections before the patient undergoes the transplant.

“Today, we know that virus-specific T-cells can help protect patients from dangerous viruses after stem cell transplants,” says Dr. Keller. “Through this research, we used the same therapy and approach, but applied it pre-transplant with the hope of providing the same benefit of protection against life-threatening viruses to patients who need it the most.”

Dr. Keller administered the VSTs from a healthy third-party donor in a five-month-old infant fighting adenovirus before undergoing a HSCT to cure him of SCID. Today, the baby is healthy and has a normal immune system. Ultimately, this research shows that the use of VSTs is likely safe in the pre-HSCT period in patients with SCID and may be an effective therapy for viral infections when they are resistant to antiviral therapy.

“I believe this VST therapy could make a real and lasting impact for patients with SCID,” said Dr. Keller. “It gives them a real chance at a long life.”

Training t-cells, essential players in the immune system, to fight a trio of viruses

Children's is the only U.S. pediatric hospital that manufactures specialized T-cells from native cord blood

What’s Known
Following treatment, patients with leukemia, lymphoma, and other cancers may receive a transplant in order to restore their body’s natural ability to fight infection and, sometimes, such transplants are a component of leukemia treatment. (Leukemia is the second most common blood cancer, after lymphoma, and its incidence rate has increased by 0.2 percent annually from 2002 to 2011.) A stem cell or cord blood transplant restores the body’s ability to produce infection-fighting white blood cells. After such transplants, however, patients can face heightened risk of developing a life-threatening infection with such viruses as adenovirus, cytomegalovirus, or Epstein-Barr virus.

What’s New
A head-to-head comparison of two strategies to thwart such viral infections shows that both approaches leverage the power of multivirus-specific, donor-derived T-cells (mCTL), which are highly skilled at recognizing foreign invaders. The research team, made up of nine scientists and clinicians affiliated with Children’s National Health System, grew personalized T-cells from peripheral blood (PB) of adult donors who were seropositive for CMV and also coaxed T-cells to grow from naïve cord blood (CB). PB-derived cells have long memories of past battles; naïve CB-derived cells need additional training to acquire such skills. From 35 to 384 days after their stem cell or cord blood transplant, 13 patients were infused with PB mCTL and 12 patients were infused with CB mCTL. Within four weeks, patients experienced up to a 160-fold increase in virus-specific T-cells, which coincided with their response to therapy. Overall response rate was 81 percent.

Questions for Future Research
Q: Could T-cells be personalized to attack other viruses that infect patients post-transplant, such as human parainfluenza virus and BK polyomavirus, providing the potential to target five viruses in a single infusion?
Q: Could the proteins that are used to train T-cells to attack certain viruses also be used to create a personalized approach to tumor suppression?

Source: “A Phase 1 Perspective: Multivirus-Specific T Cells From Both Cord Blood and Bone Marrow Transplant Donors.” Hanley, P., M. D. Keller, M. Martin Manso, C. Martinez, K. Leung, C.R. Cruz, C. Barese, S. McCormack, M. Luo, R.A. Krance, D. Jacobsohn, C. Rooney, H. Heslop, E.J. Shpall, and C. Bollard. Presented during the International Society for Cellular Therapy 2016 Annual Meeting, Singapore. May 26, 2016.