membrane-bound interleukin-12

Membrane-bound interleukin-12 (mbIL12) is an engineered biologic immunotherapy designed to harness the potent antitumor effects of interleukin-12 (IL-12) while minimizing its severe systemic toxicity. IL-12 is a pro-inflammatory cytokine that activates T cells and natural killer (NK) cells, but its clinical use has been limited by life-threatening side effects when administered systemically. mbIL12 is created by fusing IL-12 to a transmembrane domain (such as B7-1 TM), which anchors the cytokine to the surface of the cell that expresses it. This localization restricts IL-12 activity to the tumor microenvironment, facilitating paracrine signaling to nearby immune cells. This approach is primarily used to armor adoptive cell therapies (ACT), including tumor-infiltrating lymphocytes (TILs) and CAR-T cells. Companies like Obsidian Therapeutics have further refined this by using cytoDRiVE technology, which allows for the pharmacologic regulation of mbIL12 expression through the administration of an oral small molecule stabilizer like trimethoprim.

Other names

membrane-bound IL-12membrane-anchored interleukin-12