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

MARIA VICTORIA REGGE; ADRIAN FRIEDRICH; SOL YANEL NUÑEZ; MARÍA CECILIA SANTILLI; GISELLE GHERSI; MERCEDES BEATRIZ FUERTES; NORBERTO WALTER ZWIRNER; FLORENCIA SECCHIARI; XIMENA LUCIA RAFFO; ANDREA ZIBLAT; EVANGELINA ALMADA; CAROLINA INES DOMAICA; FERNANDO ALBERTO GOLDBAUM; NICOLAS IGNACIO TORRES; RAUL GERMAN SPALLANZANI; JESSICA MARIEL SIERRA; NICOLÁS GILIO; ROMINA PARDO; VANESA ZYLBERMAN

Mar del Plata

Congreso; LXVI REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA; 2018

Sociedad Argentina de Investigaciones Clínicas y Sociedad Argentina de Inmunologia

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