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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 [2])
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.
Reference materials:
[1] Engineering CAR T cells to deliver endogenous RNA wakes solid tumors to respond to therapy.
[2] Johnson et al, (2021) The immunostimulatory RNA RN7SL1 enables CAR-T cells to enhance autonomous and endogenous immune function, Cell, DOI: 10.
