Disialoganglioside-specific human natural killer cells are effective against drug-resistant neuroblastoma.

Seidel, Diana; Shibina, Anastasia; Siebert, Nikolai; Wels, Winfried; Reynolds, C.; Huebener, Nicole; Lode, Holger

The disialoganglioside GD2 is a well-established target antigen for passive immunotherapy in neuroblastoma (NB). Despite the recent success of passive immunotherapy with the anti-GD2 antibody ch14.18 and cytokines, treatment of high-risk NB remains challenging. We expanded the approach of GD2-specific, antibody-based immunotherapy to an application of a GD2-specific natural killer (NK) cell line, NK-92-scFv(ch14.18)-zeta. NK-92-scFv(ch14.18)-zeta is genetically engineered to express a GD2-specific chimeric antigen receptor generated from ch14.18. Here, we show that chimeric receptor expression enables NK-92-scFv(ch14.18)-zeta to effectively lyse GD2 NB cells also including partially or multidrug-resistant lines. Our data suggest that recognition of GD2 by the chimeric receptor is the primary mechanism involved in NK-92-scFv(ch14.18)-zeta-mediated lysis and is independent of activating NK cell receptor/ligand interactions. Furthermore, we demonstrate that NK-92-scFv(ch14.18)-zeta is able to mediate a significant anti-tumor response in vivo in a drug-resistant GD2 NB xenograft mouse model. NK-92-scFv(ch14.18)-zeta is an NB-specific NK cell line that has potential for future clinical development due to its high stability and activity toward GD2 NB cell lines.

GANGLIOSIDES; NEUROBLASTOMA; KILLER cells; DRUG resistance in cancer cells; CANCER immunotherapy; CHIMERIC proteins; THERAPEUTICS

Cancer Immunology, Immunotherapy, 2015, Vol 64, Issue 5, p621

0340-7004

Academic Journal

10.1007/s00262-015-1669-5