TY  - JOUR
AU  - Burger, Michael C
AU  - Forster, Marie-Therese
AU  - Romanski, Annette
AU  - Straßheimer, Florian
AU  - Macas, Jadranka
AU  - Zeiner, Pia S
AU  - Steidl, Eike
AU  - Herkt, Stefanie
AU  - Weber, Katharina
AU  - Schupp, Jonathan
AU  - Lun, Jennifer H
AU  - Strecker, Maja I
AU  - Wlotzka, Karolin
AU  - Cakmak, Pinar
AU  - Opitz, Corinna
AU  - George, Rosemol
AU  - Mildenberger, Iris C
AU  - Nowakowska, Paulina
AU  - Zhang, Congcong
AU  - Röder, Jasmin
AU  - Müller, Elvira
AU  - Ihrig, Kristina
AU  - Langen, Karl-Josef
AU  - Rieger, Michael A
AU  - Herrmann, Eva
AU  - Bönig, Halvard
AU  - Harter, Patrick
AU  - Reiss, Yvonne
AU  - Hattingen, Elke
AU  - Rödel, Franz
AU  - Plate, Karl H
AU  - Tonn, Torsten
AU  - Senft, Christian
AU  - Steinbach, Joachim P
AU  - Wels, Winfried S
TI  - Intracranial injection of NK cells engineered with a HER2-targeted chimeric antigen receptor in patients with recurrent glioblastoma.
JO  - Neuro-Oncology
VL  - 25
IS  - 11
SN  - 1522-8517
CY  - Oxford
PB  - Oxford Univ. Press
M1  - DKFZ-2023-00919
SP  - 2058-2071
PY  - 2023
N1  - 2023 Nov 2;25(11):2058-2071
AB  - Glioblastoma (GB) is incurable at present without established treatment options for recurrent disease. In this phase I first-in-human clinical trial we investigated safety and feasibility of adoptive transfer of clonal CAR-NK cells (NK-92/5.28.z) targeting HER2, which is expressed at elevated levels by a subset of glioblastomas.Nine patients with recurrent HER2-positive GB were treated with single doses of 1 x 10 7, 3 x 10 7 or 1 x 10 8 irradiated CAR-NK cells injected into the margins of the surgical cavity during relapse surgery. Imaging at baseline and follow-up, peripheral blood lymphocyte phenotyping and analyses of the immune architecture by multiplex immunohistochemistry and spatial digital profiling were performed.There were no dose-limiting toxicities, and none of the patients developed a cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. Five patients showed stable disease after relapse surgery and CAR-NK injection that lasted 7 to 37 weeks. Four patients had progressive disease. Pseudoprogression was found at injection sites in two patients, suggestive of a treatment-induced immune response. For all patients, median progression-free survival was 7 weeks, and median overall survival was 31 weeks. Furthermore, the level of CD8 + T-cell infiltration in recurrent tumor tissue prior to CAR-NK cell injection positively correlated with time to progression.Intracranial injection of HER2-targeted CAR-NK cells is feasible and safe in patients with recurrent GB. 1 x 10 8 NK-92/5.28.z cells was determined as the maximum feasible dose for a subsequent expansion cohort with repetitive local injections of CAR-NK cells.
KW  - CAR-NK cells (Other)
KW  - HER2 (Other)
KW  - adoptive immunotherapy (Other)
KW  - glioblastoma (Other)
KW  - phase I first-in-human clinical trial (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:37148198
DO  - DOI:10.1093/neuonc/noad087
UR  - https://inrepo02.dkfz.de/record/275931
ER  -