Adapter chimeric antigen receptor (AdCAR)-engineered NK-92 cells: an off-the-shelf cellular therapeutic for universal tumor targeting.
作者信息
Grote Stefan, Mittelstaet Joerg, Baden Caroline, Chan Kenneth Chun-Ho, Seitz Christian, Schlegel Patrick, Kaiser Andrew, Handgretinger Rupert, Schleicher Sabine
机构信息
Department of Hematology and Oncology, University Hospital Tuebingen, Children's Hospital, Tuebingen, Germany.
Miltenyi Biotec GmbH, Bergisch Gladbach, Germany.
出版信息
Oncoimmunology. 2020 Sep 29;9(1):1825177. doi: 10.1080/2162402X.2020.1825177.
Despite the recent success of CAR T cells targeting CD19 and CD22 in hematological malignancies, the production of CAR T cells still requires an extensive manufacturing process. The well-established NK-92 cell line provides a promising alternative to produce CAR-modified effector cells in a GMP-compliant, cost-effective way. NK-92 can be redirected against a variety of surface antigens by our adapter CAR (AdCAR) system utilizing biotinylated antibodies (bAb) as adapter molecules. Selected bAb were capable of inducing significant AdCAR NK-92-mediated lysis of non-Hodgkin lymphoma (NHL) and mantle-cell lymphoma (MCL) cell lines as well as primary MCL and chronic lymphocytic leukemia (CLL) cells. AdCAR specificity was proven using a JeKo-1 CD19/CD20 knockout antigen-loss model. Moreover, through combinations of bAb, AdCAR NK-92 cells are capable of combatting tumor antigen evasion mechanisms. In conclusion, we successfully generated the AdCAR NK-92 cell line which can be manufactured as an "off-the-shelf, on-demand" product allowing universal and tunable tumor targeting.