Toll-like receptor agonists and invariant natural killer T-cells enhance antibody-dependent cell-mediated cytotoxicity (ADCC).
huHMFG-1 (AS1402) is a humanised IgG1 against MUC1, which exerts tumour cell killing through antibody-dependent cellular cytotoxicity (ADCC) mediated by natural killer (NK) cells. Here, we explored the capacity of invariant NKT (iNKT) cells, which are known to activate NK cells, and toll-like receptor (TLR) ligands which activate both iNKT and NK cells, to enhance huHMFG-1-ADCC. Addition of iNKT cells, as well as TLR2/6, 7, 8 and 9 agonists to PBMC improved the efficacy of huHMFG-1. These results suggest that transfer of ex vivo expanded iNKT cells or TLR agonist treatment may improve the efficacy of NK cell-mediated antibody-based tumour immunotherapies.
Moreno
María
M
Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
Mol
Berber M
BM
von Mensdorff-Pouilly
Silvia
S
Verheijen
René H M
RH
von Blomberg
B Mary E
BM
van den Eertwegh
Alfons J M
AJ
Scheper
Rik J
RJ
Bontkes
Hetty J
HJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D005434:Flow Cytometry; D053804:Granzymes / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology*; D007167:Immunotherapy / Q000379:methods; D007694:Killer Cells, Natural / Q000276:immunology; D037181:Lectins, C-Type; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D018396:Mucin-1 / Q000276:immunology*; D055611:Natural Killer T-Cells / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology*; D000099192:CD69 Antigens
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D053804:Granzymes; D007074:Immunoglobulin G; D037181:Lectins, C-Type; D018396:Mucin-1; D051193:Toll-Like Receptors; D000099192:CD69 Antigens; C469215:pemtumomab