TY  - JOUR
AU  - Krämer, Christopher
AU  - Kilian, Michael
AU  - Chih, Y. C.
AU  - Kourtesakis, A.
AU  - Hoffmann, D. C.
AU  - Boschert, T.
AU  - Koopmann, P.
AU  - Sanghvi, K.
AU  - De Roia, A.
AU  - Jung, Simon
AU  - Jähne, K.
AU  - Day, B.
AU  - Shultz, L. D.
AU  - Ratliff, M.
AU  - Harbottle, R.
AU  - Green, E. W.
AU  - Will, R.
AU  - Wick, W.
AU  - Platten, M.
AU  - Bunse, Lukas
TI  - NLGN4X TCR transgenic T cells to treat gliomas.
JO  - Neuro-Oncology
VL  - 26
IS  - 2
SN  - 1522-8517
CY  - Oxford
PB  - Oxford Univ. Press
M1  - DKFZ-2023-01884
SP  - 266-278
PY  - 2024
N1  - HI-TRON / #EA:D170#LA:D170# /  2024 Feb 2;26(2):266-278
AB  - 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 
LB  - PUB:(DE-HGF)16
C6  - pmid:37715782
DO  - DOI:10.1093/neuonc/noad172
UR  - https://inrepo02.dkfz.de/record/282891
ER  -