> Details
Burger, Michael C.
[Author];
Forster, Marie-Therese
[Author];
Romanski, Annette
[Author];
Straßheimer, Florian
[Author];
Macas, Jadranka
[Author];
Zeiner, Pia S
[Author];
Steidl, Eike
[Author];
Herkt, Stefanie
[Author];
Weber, Katharina J
[Author];
Schupp, Jonathan
[Author];
Lun, Jennifer H
[Author];
Strecker, Maja I
[Author];
Wlotzka, Karolin
[Author];
Cakmak, Pinar
[Author];
Opitz, Corinna
[Author];
George, Rosemol
[Author];
Mildenberger, Iris
[Author];
Nowakowska, Paulina
[Author];
Zhang, Congcong
[Author];
Röder, Jasmin
[Author];
Müller, Elvira
[Author];
Ihrig, Kristina
[Author];
Langen, Karl-Josef
[Author];
Rieger, Michael A
[Author];
[...]
Intracranial injection of natural killer cells engineered with a HER2-targeted chimeric antigen receptor in patients with recurrent glioblastoma
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- Media type: E-Article
- Title: Intracranial injection of natural killer cells engineered with a HER2-targeted chimeric antigen receptor in patients with recurrent glioblastoma
- Contributor: Burger, Michael C. [VerfasserIn]; Forster, Marie-Therese [VerfasserIn]; Romanski, Annette [VerfasserIn]; Straßheimer, Florian [VerfasserIn]; Macas, Jadranka [VerfasserIn]; Zeiner, Pia S [VerfasserIn]; Steidl, Eike [VerfasserIn]; Herkt, Stefanie [VerfasserIn]; Weber, Katharina J [VerfasserIn]; Schupp, Jonathan [VerfasserIn]; Lun, Jennifer H [VerfasserIn]; Strecker, Maja I [VerfasserIn]; Wlotzka, Karolin [VerfasserIn]; Cakmak, Pinar [VerfasserIn]; Opitz, Corinna [VerfasserIn]; George, Rosemol [VerfasserIn]; Mildenberger, Iris [VerfasserIn]; Nowakowska, Paulina [VerfasserIn]; Zhang, Congcong [VerfasserIn]; Röder, Jasmin [VerfasserIn]; Müller, Elvira [VerfasserIn]; Ihrig, Kristina [VerfasserIn]; Langen, Karl-Josef [VerfasserIn]; Rieger, Michael A [VerfasserIn]; Herrmann, Eva [VerfasserIn]; Bonig, Halvard [VerfasserIn]; Harter, Patrick N [VerfasserIn]; Reiss, Yvonne [VerfasserIn]; Hattingen, Elke [VerfasserIn]; Rödel, Franz [VerfasserIn]; Plate, Karl [VerfasserIn]; Tonn, Torsten [VerfasserIn]; Senft, Christian [VerfasserIn]; Steinbach, Joachim Peter [VerfasserIn]; Wels, Winfried S [VerfasserIn]
- imprint: November 2023
- Published in: Neuro-Oncology ; 25(2023), 11 vom: Nov., Seite 2058-207
- Language: English
- DOI: 10.1093/neuonc/noad087
- ISSN: 1523-5866
- Identifier:
- Origination:
-
Footnote:
Online veröffentlicht: 6. Mai 2023
- Description: 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 chimeric antigen receptor (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 × 107, 3 × 107, or 1 × 108 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 2 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 × 108 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.
- Access State: Open Access