%0 Journal Article
%A Krämer, Christopher
%A Kilian, Michael
%A Chih, Y. C.
%A Kourtesakis, A.
%A Hoffmann, D. C.
%A Boschert, T.
%A Koopmann, P.
%A Sanghvi, K.
%A De Roia, A.
%A Jung, Simon
%A Jähne, K.
%A Day, B.
%A Shultz, L. D.
%A Ratliff, M.
%A Harbottle, R.
%A Green, E. W.
%A Will, R.
%A Wick, W.
%A Platten, M.
%A Bunse, Lukas
%T NLGN4X TCR transgenic T cells to treat gliomas.
%J Neuro-Oncology
%V 26
%N 2
%@ 1522-8517
%C Oxford
%I Oxford Univ. Press
%M DKFZ-2023-01884
%P 266-278
%D 2024
%Z HI-TRON / #EA:D170#LA:D170# /  2024 Feb 2;26(2):266-278
%X Neuroligin 4 X-linked (NLGN4X) harbors a human leukocyte antigen (HLA)-A2-restricted tumor-associated antigen, overexpressed in human gliomas, that was found to induce specific cytotoxic T cell responses following multi-peptide vaccination in patients with newly- diagnosed glioblastoma.T cell receptor (TCR) discovery was performed using droplet-based single cell TCR sequencing of NLGN4X-tetramer-sorted T cells post vaccination. The identified TCR was delivered to Jurkat T cells and primary human T cells (NLGN4X-TCR-T). Functional profiling of NLGN4X-TCR-T was performed by flow cytometry and cytotoxicity assays. Therapeutic efficacy of intracerebroventricular NLGN4X-TCR-T was assessed in NOD scid gamma (NSG) major histocompatibility complex (MHC) I/II knockout (KO) (NSG MHC I/II KO) mice bearing NLGN4X-expressing experimental gliomas.An HLA-A *02-restricted vaccine-induced T cell receptor specifically binding NLGN4X131-139 was applied for therapeutic use. Reactivity, cytotoxicity, and polyfunctionality of this NLGN4X-specific TCR is demonstrated in various cellular models. Intracerebroventricular administration of NLGN4X-TCR-T prolongs survival and leads to an objective response rate (ORR) of 44.4 
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:37715782
%R 10.1093/neuonc/noad172
%U https://inrepo02.dkfz.de/record/282891