Antibody-mediated inhibition of MICA and MICB shedding promotes NK cell–driven tumor immunity

Abstract

Helping NK cells find their way MICA and MICB proteins can be expressed on tumors and act as “kill me” signals to the immune system. But tumors often disguise themselves by shedding these proteins, which prevents specialized natural killer (NK) cells from recognizing and destroying the cancer. Ferrari de Andrade et al. engineered antibodies directed against the site responsible for the proteolytic shedding of MICA and MICB (see the Perspective by Cerwenka and Lanier). The approach effectively locked MICA and MICB onto tumors so that NK cells could spot them for elimination. The antibodies exhibited preclinical efficacy in multiple tumor models, including humanized melanoma. Furthermore, the strategy reduced lung cancer metastasis after NK cell–mediated tumor lysis. Science , this issue p. 1537 ; see also p. 1460