Irradiated and activated autologous PBMCs induce expansion of highly cytotoxic human NK cells in vitro.
Adoptive cell transfer of ex vivo-activated natural killer (NK) cells is a promising therapy for cancer treatment. Because of inhibitory signaling through killer immunoglobulin-like receptor (KIR)-KIR ligands, KIR-mismatched allogeneic NK cell transfer is considered to be a more effective strategy than is autologous transfer. However, purified NK cells do not expand well enough in vitro with good manufacturing practice-compliant components for clinical use. Some investigators have developed selective expansion of NK cells from peripheral blood mononuclear cells, but these cells have the risk of graft-versus-host disease in allogeneic settings because of T cells contamination. In this study, we developed a novel method for NK cell activation and expansion. Using only good manufacturing practice-compliant components and autologous feeder cells, once purified NK cells were effectively expanded (2500-fold at day 17). The expanded cells were highly purified NK cells, and the use of these cells is suitable for allogeneic transfer without the risk of graft-versus-host disease induction. Importantly, the expanded NK cells also showed enhanced cytotoxicity compared with NK cells conventionally expanded by recombinant human interleukin 2. Finally, induction of NKG2D ligand expression on feeder cells implies that the NKG2D-NKG2DL interaction may play a role in NK cell expansion. In conclusion, this method can be used to obtain NK cells for more successful allogeneic NK cell adoptive transfer for use in antitumor immune therapy.
Cancer Research Institute, Seoul National University College of Medicine and Hospital, Seoul, Korea.
Yong-Oon
YO
Ahn
Saerom
S
Kim
Tae Min
TM
Kim
Eun Young
EY
Song
Myoung Hee
MH
Park
Dae Seog
DS
Heo
D005720:Gamma Rays; D015234:HLA-A Antigens / Q000378:metabolism; D015235:HLA-B Antigens / Q000378:metabolism; D006801:Humans; D016219:Immunotherapy, Adoptive; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000166:cytology* / Q000528:radiation effects; D008024:Ligands; D008213:Lymphocyte Activation; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism; D054340:Receptors, KIR / Q000378:metabolism; D014184:Transplantation, Homologous
D015234:HLA-A Antigens; D015235:HLA-B Antigens; C527085:KLRK1 protein, human; D008024:Ligands; D055655:NK Cell Lectin-Like Receptor Subfamily K; D054340:Receptors, KIR