Immunotherapy May Reverse Type 1 Diabetes


PD-L1-based immunotherapy observed to elicit long-lasting diabetes reversal in mice.

Researchers recently cured type 1 diabetes (T1D) by infusing mice models with blood stem cells that are engineered to overproduce the PD-L1 protein, which is deficient in T1D, according to a study published by Science Translational Research.

The experimental approach was observed to dampen the autoimmune reaction against pancreatic islet cells in both humans and mice. Additionally, the infusion reversed the condition in mice models, according to the study authors.

Notably, nearly all of the mice achieved short-term reversal of diabetes, with one-third maintaining normal blood glucose levels throughout their lives, according to the study. If similar results are achieved in humans, infusions of modified blood stem cells may provide a cure for T1D.

“There’s really a reshaping of the immune system when you inject these cells,” said senior investigator Paolo Fiorina, MD.

When administered in mice, the stem cells traveled to the pancreas where insulin-producing cells are formed. The authors noted that the immunotherapy was effective regardless of whether PD-L1 production was increased via gene therapy or small molecule therapy.

Previous research has explored immunotherapy for T1D in an attempt to inhibit the body’s attack on islet cells; however, these approaches have been unsuccessful.

The authors of the current study found that autologous bone marrow transplants have been able to reboot certain patients’ immune systems but not others, according to the study.

“Blood stem cells have immune-regulatory abilities, but it appears that in mice and humans with diabetes, these abilities are impaired,” Dr Fiorina said. “We found that in diabetes, blood stem cells are defective, promoting inflammation and possibly leading to the onset of disease.”

The authors started their study by profiling the transcriptome of blood stem cells. They found that microRNAs controlling PD-L1 in mice and humans with diabetes are altered, which inhibits the production of PD-L1, according to the study.

Additionally, the authors discovered that PD-L1 has an anti-inflammatory effect on T1D, which may contribute to the efficacy of immunotherapy.

When the healthy gene for PD-L1 was introduced, the stem cells reversed diabetes in mouse models, according to the study.

The authors also found that a cocktail of interferon beta, interferon gamma, and polyinosinic-polycytidylic resulted in diabetes reversal.

“We think resolution of PD-L1 deficiency may provide a novel therapeutic tool for the disease,” said first author Moufida Ben Nasr, PhD.

These findings suggest that immunotherapy may effectively reverse T1D in adults, but additional studies are needed to determine how long the effects last and how often treatment is needed, according to the study.

“The beauty of this approach is the virtual lack of any adverse effects, since it would use the patients’ own cells,” Dr Fiorina concluded.

The authors said they are currently working to develop the approach into a small-molecule drug that modifies blood stem cells.

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