T regs are back - promising to do for autoimmunity what CAR Ts have done in cancer
A new generation of Treg cell therapies is springboarding off advances in CAR T cells and gene editing
Drug developers are giving regulatory T cells a second look as treatments for autoimmune disease. The difference this time is that they can leverage orthogonal benefits from CAR T cells in cancer, capitalizing on new tools for boosting potency and persistence, plus regulatory breakthroughs, to yield a new class of cell therapies.
Some of the tools come from gene editing, others from synthetic biology, indicating a convergence of new technologies that could lead to the first successful use of CAR T constructs outside of cancer.
Mechanistically, Tregs have the opposite effect to standard CAR T cells, serving to suppress rather than enhance immune responses. The idea is to exploit the flip-side of immuno-oncology, and counter the immune overactivation that characterizes autoimmune diseases instead of bolstering the weak immune response that exacerbates cancer.
The first generation of Tregs for autoimmune disease failed to advance because the unmodified cells weren’t potent enough and were difficult to isolate and expand.
The next generation will see Tregs engineered with CAR or TCR constructs to target them to specific cells, and modifications that enhance persistence, potency and stability.
“As immuno-oncology was a large disruptive force in oncology, I think Tregs will be the next disruptive force on the other side of immunology.
CAR Treg therapies could present a major improvement over marketed autoimmune medicines,