%0 Journal Article
%A Burger, Michael C
%A Forster, Marie-Therese
%A Romanski, Annette
%A Straßheimer, Florian
%A Macas, Jadranka
%A Zeiner, Pia S
%A Steidl, Eike
%A Herkt, Stefanie
%A Weber, Katharina
%A Schupp, Jonathan
%A Lun, Jennifer H
%A Strecker, Maja I
%A Wlotzka, Karolin
%A Cakmak, Pinar
%A Opitz, Corinna
%A George, Rosemol
%A Mildenberger, Iris C
%A Nowakowska, Paulina
%A Zhang, Congcong
%A Röder, Jasmin
%A Müller, Elvira
%A Ihrig, Kristina
%A Langen, Karl-Josef
%A Rieger, Michael A
%A Herrmann, Eva
%A Bönig, Halvard
%A Harter, Patrick
%A Reiss, Yvonne
%A Hattingen, Elke
%A Rödel, Franz
%A Plate, Karl H
%A Tonn, Torsten
%A Senft, Christian
%A Steinbach, Joachim P
%A Wels, Winfried S
%T Intracranial injection of NK cells engineered with a HER2-targeted chimeric antigen receptor in patients with recurrent glioblastoma.
%J Neuro-Oncology
%V 25
%N 11
%@ 1522-8517
%C Oxford
%I Oxford Univ. Press
%M DKFZ-2023-00919
%P 2058-2071
%D 2023
%Z 2023 Nov 2;25(11):2058-2071
%X 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.
%K CAR-NK cells (Other)
%K HER2 (Other)
%K adoptive immunotherapy (Other)
%K glioblastoma (Other)
%K phase I first-in-human clinical trial (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:37148198
%R 10.1093/neuonc/noad087
%U https://inrepo02.dkfz.de/record/275931