Membrane-tethered IL15 and IL21 use against solid tumors
Nguyen R, Doubrovina E, Mousset C, et al. Cooperative Armoring of CAR and TCR T Cells by T Cell-Restricted IL15 and IL21 Universally Enhances Solid Tumor Efficacy. Clinical Cancer Research. 2023; (doi: 10.1158/1078-0432.CCR-23-1872).
Collectively harnessing the different properties of interleukin 15 and 21 can boost the efficacy of engineered T cells against solid tumors, according to researchers. They employed mouse models of transgenic chimeric antigen receptor (CAR) and T-cell receptors (TCR) targeting solid tumors to observe the effect of membrane-tethered IL15, IL21, or IL15/IL21 on engineered T cells for use in human patients. The cytokines, self-delivered by CAR or TCR T cells, averted functional exhaustion and limited the emergence of dysfunctional natural killer (NK)-like T cells. Investigators documented enhanced regression with both IL15 and IL21 in various models, but measured the biggest antitumor effect when T cells were armored with both cytokines. The study authors note the approach, which improves the resilience and function of adoptive T cells against solid tumors, has potential in multiple disease and treatment settings.