Construction and characterization of multimeric IL-15 based molecules with CD3 binding domain

摘要

The invention features a soluble fusion protein complex comprising at least two soluble fusion proteins. For example, the first fusion protein is an anti-CD-3 antibody covalently linked to an interleukin-15 (IL-15) polypeptide or a functional fragment thereof. The second fusion protein comprises a binding domain that recognizes the disease antigen, which is covalently linked to a soluble interleukin-15 receptor alpha (IL-15Rα) polypeptide or a functional fragment thereof. One or both of the first and second fusion proteins further comprise an immunoglobulin Fc domain or a functional fragment thereof, wherein the IL-15 domain of the first fusion protein is soluble in the second fusion protein It binds to the IL-15Rα domain to form a soluble fusion protein complex. The invention further provides methods of making and using the complexes of the invention. [Selected figure] Figure 1