NK and T cell cancer vaccine targeting MICA and MICB

A protein vaccine targeting the cell surface stress markers MICA and MICB could help treat melanoma and other cancers by recruiting NK cells and T cells, which recognize the markers via NKG2D. The vaccine consisted of the α3 subunit of MICA and MICB — the site of proteolytic cleavage, which facilitates immune evasion by preventing NKG2D binding — fused to the N-terminus of ferritin from Heliobacter pylori, which forms 24-subunit particles.

In a mouse model of melanoma expressing human MICB, the vaccine decreased tumor volume and increased survival compared with a ferritin-only control, and induced CD4⁺ and CD8⁺ T cell responses against MICB, as well as MICB α3-specific antibodies that decreased MICB shedding to undetectable levels and increased MICB tumor cell surface density, while not interfering with MICB binding to NKG2D; the vaccine also increased tumor recruitment of NK cells and CD4⁺ and CD8⁺ T cells. In mice vaccinated after removal of the primary tumor, the vaccine reduced the number of lung metastases. In mouse models of melanoma with mutations that enable immune evasion by preventing expression of MHCI, MHCII or IFNGR1, the vaccine decreased tumor growth and increased survival compared with the ferritin control, with 50-75% of the mice remaining tumor free...