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Engineering strategies for generating hypoimmunogenic cells with high clinical and commercial value

By Dr. Nafees Malik, MBChB, MPhil, Annalisa M Jenkins, Jim Mellon, Dr. Gregory Bailey, MD

Allogeneic cell therapy, where patients receive cells from a “nonself donor”, is superior to autologous cell therapy using a patient's own cells. Autologous cells are higher quality, have a lower cost of manufacturing, and higher scalability for production. However, allogeneic therapy poses a considerable challenge because of the immune response mounted by a mismatch between donor and recipient human leukocyte antigens (HLA). The field of regenerative medicine will benefit from the ability to manufacture cells that don’t require the need for donor immunosuppression; i.e. “universal cells.” Three strategies to engineer these cells include: abolishing HLA class Ia/II proteins to prevent immune system rejection, expressing HLA class Ib proteins, and reducing the immunogenicity of cells through immune checkpoint manipulation. Such approaches have been used successfully to engineer cells that escaped or significantly blunted the T-cell response in vivo, showing promise for the future development of safe and effective therapies.

View the full peer-reviewed scientific paper at Future Medicine.

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