IL-15 receptor signaling

Class

Engineered tumor-infiltrating lymphocyte (TIL) cell therapy with membrane-bound IL-15

Pathway

Membrane-bound IL-15 provides autonomous cytokine support to enhance TIL persistence, proliferation and antitumor activity without requiring exogenous IL-2

Notes

original target text: IL-15 receptor signaling (via engineered membrane-bound IL-15 expressed on the TILs themselves)

IL-15 is a cytokine that supports the survival, proliferation, and functional fitness of cytotoxic T cells and natural killer cells. It signals through a receptor complex that shares components with the IL-2 receptor, but rather than being secreted broadly and binding free-floating, IL-15 is typically presented to responding cells while still attached to the membrane of another cell, a process called trans-presentation. In cell-based cancer therapies using tumor-infiltrating lymphocytes (TILs), immune cells are extracted from a tumor, expanded outside the body, and reinfused to attack cancer. Historically, these cells required repeated dosing of exogenous IL-2 after infusion to persist and remain active, but IL-2 administration causes significant systemic toxicity and can inadvertently expand regulatory T cells that suppress antitumor immunity. Engineering the TILs themselves to express a membrane-bound form of IL-15 allows the cells to stimulate their own IL-15 receptor signaling locally and continuously, supporting persistence and proliferation without depending on external cytokine infusions. This approach broadly matters in solid tumor immunotherapy, where TIL survival and functional durability after transfer is a limiting factor in achieving lasting antitumor responses.