CAR-T therapy has not yet shown significant efficacy in the treatment of solid tumors.
Poor tumor invasion, T cell exhaustion and uneven expression of tumor cell antigens are common reasons that limit the efficacy of CAR-T cells
Recently, a team led by Professor Carl June and Andy J.
Minn of the University of Pennsylvania published their latest research in the top scientific journal Cell
Scientists have equipped CAR-T cells with two new "weapons".
"Usually CAR-T cells are fighting alone when they kill tumors
Our research shows that given the right "weapons", they can activate the body's own immune system and help them fight tumor cells
The first "weapon" that researchers put on CAR-T cells was RNA called RN7SL1
This RNA is derived from the body's own cells, but when delivered to the vicinity of the tumor by CAR-T cells, they can mimic viral RNA
The second "weapon" for CAR-T cells is to allow them to express foreign antigens
These antigens can be released through extracellular vesicles (EV) and fused with tumor cells, just like "coating" a layer of foreign antigens on the surface of tumor cells, helping endogenous T cells in the body to recognize and kill tumor cells
▲Illustration of this research (picture source: reference )
In a mouse model, experiments have shown that adding these two "weapons" to CAR-T cells can activate the body's immune system.
Even if the imported CAR-T cells themselves cannot recognize all tumor cells, they can still prevent tumor recurrence
In addition, the experimental results show that RN7SL1 can also improve the function of CAR-T cells.
CAR-T cells expressing RN7SL1 have better persistence, stronger tumor infiltration, and the ability to kill tumors for longer
"While using CAR-T cells, enhancing the function of endogenous T cells and counteracting common immunosuppressive mechanisms can provide a combined strategy to improve the response of patients with solid tumors
" Co-corresponding author of this study, University of Pennsylvania Cell Said Dr.
 Engineering CAR T cells to deliver endogenous RNA wakes solid tumors to respond to therapy.
 Johnson et al, (2021) The immunostimulatory RNA RN7SL1 enables CAR-T cells to enhance autonomous and endogenous immune function, Cell, DOI: 10.