Helmholtz Gemeinschaft


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

Item Type:Article
Title:Disialoganglioside-specific human natural killer cells are effective against drug-resistant neuroblastoma
Creators Name:Seidel, D. and Shibina, A. and Siebert, N. and Wels, W.S. and Reynolds, C.P. and Huebener, N. and Lode, H.N.
Abstract: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.
Keywords:Neuroblastoma GD2, Chimeric Antigen Receptor, Natural Killer Cell, Single-Chain Antibody
Source:Cancer Immunology Immunotherapy
Page Range:621-634
Date:May 2015
Official Publication:https://doi.org/10.1007/s00262-015-1669-5
PubMed:View item in PubMed

Repository Staff Only: item control page

Open Access
MDC Library