Tethered Interleukin-15 (IL-15)/IL-21 to Enhance T Cells for Cellular Therapy

Interleukin-15 (IL-15) and IL-21 have been reported to support the function of anti-tumor T cells.  However, their use in the clinic has been constrained, in part, by dose-limiting toxicity and the need for repeated administration.  To overcome these limitations, researchers in the National Cancer Institute (NCI) Experimental Transplantation and Immunology Branch (ETIB) have developed synthetic IL-15 and IL-21 molecules for autocrine expression by the engineered therapeutic T cells. These molecules were designed with flexible linkers that connect to cell membrane anchors.  This, in turn, reduces systemic toxicity caused by free cytokine molecules. The inventors have shown that co-expression of the novel IL-15 and IL-21 tethered molecules improves the anti-tumor efficacy of the therapeutic engineered T cells in vivo. 

Competitive Advantages:

• T cells that co-express the tethered IL-15 and IL-21 on their cell membrane can increase therapeutic effectiveness of adoptive immunotherapy because it can reduce systemic toxicity caused by free cytokine molecules
• T cells that co-express the tethered IL-15 and IL-21 on their cell membrane are already known to have a greater decrease in tumor size compared to those mice treated with T cell-based immunotherapies using unmodified T cells 

Commercial Applications:

• Treatment of cancer patients receiving T cell-based immunotherapy