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Innovative Immune Cell Technology Offers Hope for Transplant and Autoimmune Treatment
Researchers at UC San Francisco have made a significant advancement in immune cell technology that could enhance treatments for organ transplants, type 1 diabetes, and other autoimmune disorders. This development aims to address the complications arising from an overactive immune response.
When the immune system becomes overly aggressive, it can mistakenly target and damage the body’s own tissues, leaving patients with no recourse but to suppress their immune response altogether. This suppression, however, often increases the risk of infections and certain cancers.
The novel approach developed by UCSF scientists utilizes engineered T cells designed to act as immune “referees.” These referees can mitigate excessive immune reactions and eliminate inflammatory substances from the body.
This innovative technique has the potential to prevent organ and tissue rejection, particularly in transplants involving pancreatic islet cells, which are crucial for treating type 1 diabetes. Current treatments often require patients to take potent immunosuppressive medications, which carry their own risks and side effects.
“This technology can put the immune system back into balance,” explained Wendell Lim, PhD, a professor at UCSF and co-senior author of a paper published in Science on December 5. “We see it as a potential platform for tackling all kinds of immune dysfunction.”
The research team drew inspiration from the body’s natural “suppressor” cells, which are intended to regulate and tone down immune responses. Despite their role, these suppressor cells sometimes fail to counteract harmful immune attacks, such as in the case of type 1 diabetes, where they are ineffective against the destruction of pancreatic islet cells.
To overcome this limitation, the UCSF researchers repurposed the anti-inflammatory properties of suppressor cells into CD4 immune cells, which are also instrumental in creating CAR T cells used in cancer therapy. Additionally, they equipped these modified cells with molecular sensors to target specific tissues within the body.
Proof of Concept in Type 1 Diabetes
The scientists created a custom batch of these immune referees engineered to seek out human pancreatic islet cells. Once located, these cells produce TGF-Beta and CD25, molecules that restrain harmful T cells from launching attacks.
In experimental trials, the team introduced these engineered cells into mice that had undergone transplantation of human islet cells, simulating a treatment model for type 1 diabetes. The immune referees successfully identified the vulnerable islet cells and inhibited the attack from killer T cells, allowing the islet cells to survive.
“It would be life changing for people with type 1 diabetes if they could receive new islet cells without needing to take immunosuppressants and avoid daily insulin injections,” noted Audrey Parent, PhD, an associate professor in the UCSF Diabetes Center and co-senior author of the study.
Looking ahead, Lim envisions a medical landscape where organ transplant recipients or individuals with autoimmune diseases can receive targeted therapies that solely address the problematic areas of the immune system. This strategy could mitigate the serious side effects associated with broad-spectrum immunosuppressants, thereby reducing the risk of opportunistic infections and cancers linked to comprehensive immune suppression.
Moreover, this technology could enhance the precision of CAR T cell therapies in cancer treatment, enabling these engineered cells to differentiate between malignant tumors and healthy tissue.
“This opens up numerous possibilities for addressing major medical challenges,” stated Lim, who leads the UCSF Cell Design Institute. “We hope to see this technology benefiting patients in the near future.”
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