% IMPORTANT: The following is UTF-8 encoded. This means that in the presence % of non-ASCII characters, it will not work with BibTeX 0.99 or older. % Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or % “biber”. @ARTICLE{Krmer:282891, author = {C. Krämer$^*$ and M. Kilian$^*$ and Y. C. Chih$^*$ and A. Kourtesakis$^*$ and D. C. Hoffmann$^*$ and T. Boschert$^*$ and P. Koopmann$^*$ and K. Sanghvi$^*$ and A. De Roia$^*$ and S. Jung$^*$ and K. Jähne$^*$ and B. Day and L. D. Shultz and M. Ratliff and R. Harbottle$^*$ and E. W. Green$^*$ and R. Will$^*$ and W. Wick$^*$ and M. Platten$^*$ and L. Bunse$^*$}, title = {{NLGN}4{X} {TCR} transgenic {T} cells to treat gliomas.}, journal = {Neuro-Oncology}, volume = {26}, number = {2}, issn = {1522-8517}, address = {Oxford}, publisher = {Oxford Univ. Press}, reportid = {DKFZ-2023-01884}, pages = {266-278}, year = {2024}, note = {HI-TRON / #EA:D170#LA:D170# / 2024 Feb 2;26(2):266-278}, abstract = {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 $\%$ in experimental gliomas-bearing NSG MHC I/II KO mice compared to 0.0 $\%$ in control groups, respectively.NLGN4X-TCR-T demonstrates efficacy in a preclinical glioblastoma model. On a global scale, we provide first evidence for the therapeutic retrieval of vaccine-induced human TCRs for the off-the-shelf treatment of glioblastoma patients.}, cin = {D170 / HD01 / B320 / F160 / W111}, ddc = {610}, cid = {I:(DE-He78)D170-20160331 / I:(DE-He78)HD01-20160331 / I:(DE-He78)B320-20160331 / I:(DE-He78)F160-20160331 / I:(DE-He78)W111-20160331}, pnm = {314 - Immunologie und Krebs (POF4-314)}, pid = {G:(DE-HGF)POF4-314}, typ = {PUB:(DE-HGF)16}, pubmed = {pmid:37715782}, doi = {10.1093/neuonc/noad172}, url = {https://inrepo02.dkfz.de/record/282891}, }