What if genetically enhanced cells could scavenge toxic substances from the blood of patients with metabolic disorders, relieving them of the challenge of daily enzyme injections and problematic immune responses?
To realize these and many more possibilities, researchers must develop finely tuned cellular machines that can thrive inside the body while evading destruction by the immune system. Such is the goal of two approaches currently under development at Flagship Pioneering companies. One of these arms red blood cells with therapeutic proteins to treat disease while calming an overactive immune system. The other implants capsules of medicine-producing cells into a patient's body.
These experimental treatments build on more than 200 years of experience with cell transplantation. In 1825, James Blundell performed the first successful cell transplants by transfusing blood to a woman dying of postpartum hemorrhage. In 1954, a kidney transplant between identical twin brothers marked the first successful solid organ transplantation. The first successful stem-cell transplant occurred two years later, also between identical twins. By 2017, a series of advances had enabled the development and approval of immune cells known as CAR-Ts. The first CAR-Ts were launched as powerful new treatments for leukemia, and efforts to evaluate them as treatments for other cancers continue apace.
Over these two centuries of progress, researchers have learned how to keep finicky cells alive during production, through delivery, and well after they are administered to patients. Transplanted cells can be incredibly powerful, if sensitive to small changes in their environment. But the most daunting hurdle for this form of therapy is the potential for a recipient’s body to view transplanted cells as dangerous outsiders that require elimination. In a worst-case scenario, the patient’s immune system may not only destroy a transplant but respond in a way that proves life threatening or even fatal.
