Targeted cellular therapy with natural killer cells.
Natural killer (NK) cells are believed to be important contributors to a patient's immune armamentarium to fight cancer. However, cancer patients have reportedly defective NK cells and the malignant target frequently has developed mechanisms to escape detection of NK cells. Our research is aimed at overcoming this NK cell paralysis through three different approaches: instead of using autologous NK cells for adoptive immunotherapy, allogeneic NK cells are used that are not inhibited by self histocompatibility antigens. Further, NK cells, selected for a high affinity Fc receptor can, together with monoclonal antibodies, kill targets through ADCC irrespective of any inhibitory receptors. Finally, the genetic engineering of NK cells to express chimeric antigen receptors recognizing antigens on tumor target can overcome inhibitory mechanism and effectively lyse tumor cells.
Klingemann
H
H
Tufts-New England Medical Center, Boston, MA 02111, USA. hklingemann@tufts-nemc.org
Boissel
L
L
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive; D007694:Killer Cells, Natural / Q000276:immunology* / Q000637:transplantation; D051379:Mice; D050506:Mutant Chimeric Proteins / Q000276:immunology; D009369:Neoplasms / Q000628:therapy; D011946:Receptors, Antigen / Q000276:immunology
D000911:Antibodies, Monoclonal; D050506:Mutant Chimeric Proteins; D011946:Receptors, Antigen