%0 Journal Article
%A Kourtesakis, Alexandros
%A Bailey, Eileen
%A Chow, Hiu Nam Hannah
%A Rohdjeß, Hannah
%A Mussnig, Normann
%A Agardy, Dennis Alexander
%A Hoffmann, Dirk Carsten Frieder
%A Chih, Yu-Chan
%A Will, Rainer
%A Kaulen, Leon
%A Hahn, Melissa
%A Wagener, Robin
%A Reibold, Denise
%A Pusch, Sonja
%A Sahm, Felix
%A Sauer, Tim
%A Schmitt, Michael
%A Bunse, Lukas
%A Platten, Michael
%A Wick, Wolfgang
%A Kessler, Tobias
%T Utilization of universal-targeting mSA2 CAR-T cells for the treatment of glioblastoma.
%J OncoImmunology
%V 14
%N 1
%@ 2162-4011
%C Abingdon
%I Taylor & Franics
%M DKFZ-2025-01246
%P 2518631
%D 2025
%Z #EA:B320#LA:B320#
%X Glioblastoma (GB) remains refractory to chimeric antigen receptor (CAR)-T cell therapy, mainly attributed to tumor heterogeneity and antigen escape. CAR-T cells utilizing monomeric streptavidin-2 (mSA2) instead of a traditional target binding domain, bind biotinylated antibodies and can be directed to variable targets to mediate anti-tumor effects. Although such an approach might circumvent the aforementioned challenges, the potential of mSA2 CAR-T cells for brain tumor treatment remains unexplored. In this study, we generated mSA2 CAR-T cells and tested their efficacy against GB by tailoring their specificity toward GB-associated markers CD276, EPHA2, CD70 and IL13Ra2. In vitro, mSA2 CAR-T cells specifically recognized multiple primary GB cell lines in a target- and biotinylated antibody-dependent manner. Moreover, in heterogenous tumor environments, mSA2 CAR-T cells simultaneously targeted multiple subpopulations, guided by combinations of biotinylated antibodies, indicating their potential to address tumor heterogeneity. Finally, the mSA2 CAR-T cell-mediated anti-tumor functions were demonstrated in vivo. Immunocompromised mice orthotopically implanted with CD70+ or CD276+ GB cells and treated with mSA2 CAR-T cells pre-armed with antibodies against these two antigens exhibited control of tumor growth and induction of GB cell apoptosis after therapy. Taken together, our study suggests that antibody-guided mSA2 CAR-T cells can target potentially any surface GB-related antigen both in vitro and in vivo, either univalently or multivalently, with underlined clinical implications.
%K Glioblastoma: therapy
%K Glioblastoma: immunology
%K Glioblastoma: pathology
%K Animals
%K Humans
%K Mice
%K Immunotherapy, Adoptive: methods
%K Brain Neoplasms: therapy
%K Brain Neoplasms: immunology
%K Brain Neoplasms: pathology
%K Receptors, Chimeric Antigen: immunology
%K Receptors, Chimeric Antigen: metabolism
%K Receptors, Chimeric Antigen: genetics
%K Cell Line, Tumor
%K Xenograft Model Antitumor Assays
%K T-Lymphocytes: immunology
%K T-Lymphocytes: metabolism
%K Glioblastoma (Other)
%K immunotherapy (Other)
%K mSA2 CAR-T cells (Other)
%K universal antigen targeting (Other)
%K Receptors, Chimeric Antigen (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:40518621
%R 10.1080/2162402X.2025.2518631
%U https://inrepo02.dkfz.de/record/302114