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MHC Class I–Related Chain A Conjugated to Antitumor Antibodies Can Sensitize Tumor Cells to Specific Lysis by Natural Killer Cells

Authors' Affiliations: ¹ INSERM, EMI0227, Centre de Recherche en Cancérologie de Montpellier, Centre Régional de Lutte contre le Cancer Val d'Aurelle-Paul Lamarque, Montpellier, France; ² Biochemistry Institute and ³ Ludwig Institute for Cancer Research, University of Lausanne, Epalinges, Switzerland

Requests for reprints: Bruno Robert, INSERM, EMI0227, Centre de Recherche en Cancérologie de Montpellier, Centre Régional de Lutte contre le Cancer Val d'Aurelle-Paul Lamarque, 34298 Montpellier, France. Phone: 33-467-613-708; Fax: 33-467-613-787; E-mail: brobert{at}valdorel.fnclcc.fr.

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 NKG2D 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.

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