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


METHODS
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.
Germain
Claire
C
INSERM, EMI0227, Centre de Recherche en Cancérologie de Montpellier, Centre Régional de Lutte contre le Cancer Val d'Aurelle-Paul Lamarque, Montpellier, France.
Larbouret
Christel
C
Cesson
Valérie
V
Donda
Alena
A
Held
Werner
W
Mach
Jean-Pierre
JP
Pèlegrin
André
A
Robert
Bruno
B
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology; D000912:Antibodies, Neoplasm / Q000737:chemistry / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology; D002460:Cell Line; D045744:Cell Line, Tumor; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000737:chemistry*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology / Q000473:pathology
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D015395:Histocompatibility Antigens Class I; D007140:Immunoglobulin Fab Fragments; C099187:MHC class I-related chain A