Duping antibodies with a decoy, researchers aim to prevent rejection of transplanted cells

Researchers at UCSF have developed a novel, potentially life-saving approach that may prevent antibodies from triggering immune rejection of engineered therapeutic and transplant cells.

The new strategy, described in the issue of Nature Biotechnology, involved using a “decoy” receptor to capture the antibodies and take them out of circulation before they could kill the therapeutic cells, that they treat as invading foreigners. The tactic may also be useful for organ transplants.

The most celebrated cellular therapies are chimeric antigen receptor (CAR) T-cell therapies. These CAR-T therapies are often used to successfully treat specific forms of lymphomas, a type of often-deadly cancer. But deploying them against solid tumors has proved much more difficult.

Until recently, most CAR-T therapies have been made using the patient’s own cells, but the long-term commercial viability of cellular therapies of all types will rely on “allogeneic” cells - mass-produced therapeutic cells grown from a source outside the patient.

The researchers genetically engineered three types of cells-insulin-producing pancreatic islet cells, thyroid cells, and CAR-T cells-so that each type made and displayed large numbers of a protein called CD64 on their surfaces.

On these engineered cells, CD64, which tightly binds the antibodies responsible for this type of immune rejection, acted as a kind of decoy, capturing the antibodies and binding them to the engineered cell, so they wouldn’t activate immune cells.

While such cells are biologically sophisticated, they are also expensive and hard to manufacture. This would make treatment with cellular therapies cheaper and more accessible, putting them within reach for many more patients.

Reference:

Duping antibodies with a decoy, researchers aim to prevent rejection of transplanted cells; Nature Biotechnology