MHC class I-related chain a conjugated to antitumor antibodies can sensitize tumor cells to specific lysis by natural killer cells

Abstract

Purpose: As a first step for the development of a new cancer immunotherapy strategy, we evaluated whether antibody-mediated coating by MHC class I - related chain A (MICA) could sensitize tumor cells to lysis by natural killer (NK) cells. Experimental Design: Recombinant MICA (rMICA) was chemically conjugated to Fab fragments from monoclonal antibodies specific for tumor-associated antigens, such as carcinoembryonic antigen, HER2, or CD20. Results: Flow cytometry analysis showed an efficient coating of MICA-negative human cancer cell lines with the Fab-rMICA conjugates. This was strictly dependent on the expression of the appropriate tumor-associated antigens in the target cells. Importantly, preincubation of the tumor cells with the appropriate Fab-rMICA conjugate resulted in NK cell - mediated tumor cell lysis. Antibody blocking of the NKG 2D receptor in NK cells prevented conjugate-mediated tumor cell lysis. Conclusions: These results open the way to the development of immunotherapy strategies based on antibody-mediated targeting of MICA. © 2005 American Association for Cancer Research.