Restoration of anti-tumor immunity through anti-MICA antibodies elicited with a chimeric protein

TORRES NI, REGGE MV, LAUCHE C, PARDO R, DOMAICA CI, FUERTES MB, MADAUSS KP, HANCE KW, GLOGER I, ZYLBERMAN V, GOLDBAUM FA AND ZWIRNER NW

Journal for ImmunoTherapy of Cancer

Springer Nature

Lugar: Londres; Año: 2020

2051-1426

Natural killer and cytotoxic CD8+ 44 T cells are major players during tumor immunity. They express NKG2D, an activating receptor that promotes tumor elimination through recognition of the MHC class I chain-related proteins A and B (MICA and MICB). However, tumors shed MICA and soluble MICA (sMICA) mediates tumor immune escape. As anti-MICA antibodies (Ab) may promote the restoration of tumor immunity, we generated a highly immunogenic chimeric protein (BLS-MICA) consisting of MICA fused to the lumazine synthase from Brucella spp. (BLS) and used it to investigate if anti-MICA Ab can reinstate tumor immunity. Immunization with BLS-MICA and administration of anti-MICA Ab elicited by BLS-MICA significantly delayed the growth of MICA-expressing tumors. Its therapeutic effect included scavenging of sMICA and induction of Ab that mediated Ab-dependent cell-mediated cytotoxicity,higher intra-tumoral M1/pro-inflammatory macrophages and antigen-experienced CD8+ T cells. Therefore, BLS-MICA reinstates anti-tumor immunity and constitutes a promising therapeutic tool for cancer patients.