interleukin-15 fusion protein BJ-001

A human fusion protein composed of the cytokine interleukin (IL)-15 linked with an integrins-targeting moiety, with potential antineoplastic activity. Upon subcutaneous administration, the integrins-targeting moiety of BJ-001 targets tumor cells that overexpress integrins such as alpha v beta 3 (avb3), alpha v beta 5 (avb5) and alpha v beta 6 (avb6) and the IL-15 moiety binds to the IL-2/IL-15 receptor beta-common gamma chain (IL-2Rbetagamma) receptor on natural killer (NK) cells and CD8+ T lymphocytes. This activates and increases the levels of NK cells and memory CD8+ T cells. The memory T cells enhance the secretion of the cytokine interferon-gamma (IFN-g), which further potentiates the immune response against tumor cells. This may increase tumor cell killing and decrease tumor cell proliferation. IL-15 regulates CD8+ T- and NK cell development, activation and proliferation. Integrins are involved in tumor growth, angiogenesis, and metastasis and they are overexpressed in a variety of tumor cell types. The linkage of the two moieties may limit the effects of IL-15 to the local tumor microenvironment (TME), increasing efficacy while reducing systemic toxicities.