Journal Article

DKFZ-2023-00919

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Intracranial injection of NK cells engineered with a HER2-targeted chimeric antigen receptor in patients with recurrent glioblastoma.

Burger, M. C. ; Forster, M.-T. ; Romanski, A. ; Straßheimer, F. ; Macas, J.DKFZ* ; Zeiner, P. S. ; Steidl, E. ; Herkt, S. ; Weber, K.DKFZ* ; Schupp, J.DKFZ* ; Lun, J. H.DKFZ* ; Strecker, M. I. ; Wlotzka, K. ; Cakmak, P.DKFZ* ; Opitz, C. ; George, R.DKFZ* ; Mildenberger, I. C. ; Nowakowska, P. ; Zhang, C. ; Röder, J. ; Müller, E. ; Ihrig, K. ; Langen, K.-J. ; Rieger, M. A.DKFZ* ; Herrmann, E. ; Bönig, H. ; Harter, P.DKFZ* ; Reiss, Y.DKFZ* ; Hattingen, E. ; Rödel, F.DKFZ* ; Plate, K. H.DKFZ* ; Tonn, T.DKFZ* ; Senft, C. ; Steinbach, J. P. ; Wels, W. S.DKFZ*

2023
Oxford Univ. Press Oxford

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Please use a persistent id in citations: doi:10.1093/neuonc/noad087

Abstract: 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.

Keyword(s): CAR-NK cells ; HER2 ; adoptive immunotherapy ; glioblastoma ; phase I first-in-human clinical trial

Note: 2023 Nov 2;25(11):2058-2071

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Contributing Institute(s):

1. DKTK Koordinierungsstelle Frankfurt (FM01)
2. DKTK Koordinierungsstelle Dresden (DD01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2023

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Database coverage:
; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Essential Science Indicators ; IF >= 15 ; JCR ; Nationallizenz ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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