Monica Bertagnolli: Could Engineered Immune Cells Be Used to Treat People with Autoimmune Diseases and Organ Transplants

Monica Bertagnolli, Director of the National Institutes of Health (NIH), posted on LinkedIn:

“Millions of people in the U.S. have an autoimmune disease, from type 1 diabetes to inflammatory bowel disease, in which the immune system attacks the body’s own organs, tissues, or cells to cause damage. While treatments that tamp down the immune system can help, they can increase risk for infection or cancer due to systemic immune suppression. Similarly, for people who’ve received an organ or tissue transplant, immunosuppressants used to prevent rejection can leave the whole body vulnerable. What if there was a way to suppress the immune system only right where it’s needed, in tissues or organs at risk for immune attack?

An NIH-supported study reported in Science describes a way to do just that by using a cell-based therapy approach. The therapeutic approach involves taking a blood sample from a patient, modifying certain immune cells in the laboratory, and then reintroducing the engineered cells back into the body. Such cell-based therapeutics can be designed to recognize specific molecules to target tissues. This approach is already used to treat many cancers, utilizing a patient’s own engineered immune cells, known as CAR T cells, to attack and kill their cancer. Inspired by the success of the CAR T-cell example, the researchers behind this new work see the technology they’re developing as a potential platform for tackling many types of immune dysfunction.

In the new study, the team, led by Wendell Lim and Audrey Parent , both at the University of California, San Francisco, started by engineering human CD4+ T cells to become ‘immunosuppressive’ by releasing molecules that could act as brakes on the immune system. The researchers also gave these cells a molecular sensor to guide them to the target tissue in the body and to only produce the immunosuppressive molecules when they were in the target tissue.

They found that the engineered immune suppressor cells worked best when they also produced anti-inflammatory signals and receptors to bind and clear away molecules that would otherwise encourage inflammation. Looking at mouse models of type 1 diabetes, the researchers found that the engineered suppressor cells successfully protected transplanted pancreatic islet cells against an immune attack. Pancreatic islets are cells in the pancreas that make hormones, including insulin, to control blood sugar.

That’s important because the loss of pancreatic islet cells in type 1 diabetes leads to insulin deficiency. While transplants of islet cells can restore insulin production to reverse diabetes, recipients must take immunosuppressive medication to prevent a rejection. When the researchers introduced the engineered suppressor cells into mice that had received a transplant of human islet cells, the engineered cells protected the vulnerable islet cells from an attack by the killer T cells. The new findings therefore suggest it could one day be possible to transplant new islet cells into patients without requiring them to take immunosuppressants that affect the whole body.

While much more study is needed, the researchers suggest that such synthetic suppressor T cells could serve as a readily customizable platform to potentially treat many autoimmune conditions. Engineered immune suppressor cells could also be used to fine-tune CAR T-cell therapies for cancer so that they only attack tumors and not normal tissues, making them less toxic. This paves the way for a future in which there may be many more possibilities for precisely tamping down the immune system in ways that could prove life-changing for transplant recipients and those with type 1 diabetes, as well as many other autoimmune conditions.”

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Monica Bertagnolli is the Director of the National Institutes of Health (NIH), USA. She is the President of Alliance for Clinical Trials In Oncology Foundation. She previously served as the Richard E. Wilson Professor of Surgery in the field of surgical oncology at Harvard Medical School, a surgeon at Brigham and Women’s Hospital, and a member of the Gastrointestinal Cancer Treatment and Sarcoma Centers at Dana-Farber Cancer Institute. Dr. Bertagnolli is the Founding Chair of the minimal Common Oncology Data Elements (mCODE) executive committee and has held multiple positions nationally, including being Past President and Chair of the Board of Directors of the American Society of Clinical Oncology. In 2021, she was elected to the National Academy of Medicine, having previously served on the National Academies National Cancer Policy Forum.