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

REGGE, MARÍA VICTORIA; TORRES, NICOLÁS IGNACIO; SECCHIARI, FLORENCIA; FRIEDRICH, ADRIÁN; SPALLANZANI, RAÚL GERMÁN; RAFFO IRAOLAGOITÍA, XIMENA LUCÍA; NÚÑEZ, SOL YANEL; SIERRA, JESSICA MARIEL; ZIBLAT, ANDREA; SANTILLI, MARÍA CECILIA; GILIO, NICOLÁS; ALMADA, EVANGELINA; GHERSI, GISELLE; PARDO, ROMINA PAOLA; DOMAICA, CAROLINA INÉS; FUERTES, MERCEDES BEATRIZ; ZYLBERMAN, VANESA; GOLDBAUM, FERNANDO ALBERTO; ZWIRNER, NORBERTO WALTER

Mar del Plata

Congreso; 66ª Reunión Anual de la Sociedad Argentina de Inmunología; 2018

Sociedad Argentina de Inmunología

To overcome tumor immune escape and eradicate established tumors and metastases constitutes a pending challenge in immuno-oncology. Natural killer and cytotoxic CD8+ 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) over-expressed on tumor cells. However, tumors shed MICA and mediate 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. Active immunization with BLS-MICA and passive administration of anti-MICA Ab triggered by BLS-MICA in C57BL/6 mice significantly delayed the growth of MICA-expressing tumors (n=14, p