COVID-19 Resource Center
COVID-19 Resource Center
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Disclosures: Gladstone reports no relevant financial disclosures.
September 08, 2020
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Regulatory T-cell therapy shows promise for COVID-19-related respiratory distress

Source/Disclosures
Disclosures: Gladstone reports no relevant financial disclosures.
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The COVID-19 pandemic has created unprecedented challenges for the scientific community.

Researchers are “scrambling to come up with answers” in their quest to identify optimal strategies to treat and prevent the novel coronavirus, according to Douglas E. Gladstone, MD, clinical director of the outpatient blood and marrow program at Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins.

Source: Adobe Stock.

One option may come in the form of regulatory T (Treg) cells, which the body naturally produces to diminish inflammatory responses and begin the process of tissue repair.

Douglas E. Gladstone, MD
Douglas E. Gladstone

Gladstone and colleagues published a case study published in Annals of Internal Medicine that detailed their use of Tregs to treat two patients with acute respiratory distress syndrome resulting from COVID-19 infection.

Healio spoke with Gladstone about the research, as well as the therapeutic potential of Treg cells and plans for their future use.

Question: Can you explain the rationale for this approach?

Answer: The normal function of regulatory T cells is to dampen the body’s immune response. Early in an infection, while there is an inflammatory state, Treg cells also are produced. The inhibitory signal basically starts at the same time as the inflammatory signal and the body stays in balance. In patients with severe COVID-19 infection, Treg cells as a whole are markedly decreased, and that is why many of us believe there is such an intense inflammatory response.

The main problem with severe COVID-19 infection is the inflammatory response leading to intubation; a more severe inflammatory response can lead to low blood pressure and multisystem organ failure. The rationale behind our approach was whether we could replace naturally occurring Treg cells from an exogenous source.

Q: The regulatory T cells were administered as part of the compassionate use protocol. What was their intended indication?

A: These cells have been studied in other inflammatory conditions but never for COVID-19, so there was no protocol for their use in treating COVID-19. We thought that Treg cells could be useful in this case, so we applied for a compassionate use waiver from the FDA The process also involved our internal review board at Johns Hopkins. Both bodies thought the approach was warranted and they approved the single use of Treg cells for two patients.

Q: How confident are you that Treg cell therapy had a significant role in both patients’ recovery?

A: I’m cautiously optimistic. Many of the interventions we tried were started before the Treg infusions. Despite multiple interventions, there was no marked improvement for either patient. We plan to start a randomized, placebo-controlled, multi-institutional trial to determine if Treg cells are responsible for improving symptoms of acute respiratory distress syndrome among patients with COVID-19.

Many institutions and researchers are scrambling to come up with answers to this pandemic. One of the largest problems with current COVID-19 research is that much of it is observational reporting or anecdotal rather than randomized, placebo-controlled study data. This was much like we saw during the Ebola outbreak. Looking back, we still do not know what worked and what didn’t work.

The only way to determine whether Treg cells are effective for treating the respiratory symptoms of COVID-19 is through a placebo-controlled, randomized trial. We are moving ahead with the protocol so, clearly, I believe they had a direct effect, but that is yet to be determined.

Q: At what point in the disease course would patients in the trial receive this treatment?

A: The trial will offer Treg cells to patients who have been intubated for 120 hours — 5 days — or less. Enrolled patients will need to be intubated because of severe pulmonary distress, and they must have COVID-19. Because so many people are critically ill with this disease, we are attempting to include as many people as possible, so there are no other major exclusion or inclusion criteria. We have received institutional review board approval to start the trial protocol and hope to begin enrollment in late September.

For more information:

Douglas E. Gladstone, MD, can be reached at Sidney Kimmel Comprehensive Cancer Center, 1650 Orleans St., CRB1-288, Baltimore, MD 21287; email: dgladst1@jhmi.edu.