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@ARTICLE{Kourtesakis:302114,
author = {A. Kourtesakis$^*$ and E. Bailey$^*$ and H. N. H. Chow$^*$
and H. Rohdjeß$^*$ and N. Mussnig$^*$ and D. A. Agardy$^*$
and D. C. F. Hoffmann$^*$ and Y.-C. Chih$^*$ and R. Will$^*$
and L. Kaulen$^*$ and M. Hahn$^*$ and R. Wagener$^*$ and D.
Reibold$^*$ and S. Pusch$^*$ and F. Sahm$^*$ and T. Sauer
and M. Schmitt and L. Bunse$^*$ and M. Platten$^*$ and W.
Wick$^*$ and T. Kessler$^*$},
title = {{U}tilization of universal-targeting m{SA}2 {CAR}-{T} cells
for the treatment of glioblastoma.},
journal = {OncoImmunology},
volume = {14},
number = {1},
issn = {2162-4011},
address = {Abingdon},
publisher = {Taylor $\&$ Franics},
reportid = {DKFZ-2025-01246},
pages = {2518631},
year = {2025},
note = {#EA:B320#LA:B320#},
abstract = {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.},
keywords = {Glioblastoma: therapy / Glioblastoma: immunology /
Glioblastoma: pathology / Animals / Humans / Mice /
Immunotherapy, Adoptive: methods / Brain Neoplasms: therapy
/ Brain Neoplasms: immunology / Brain Neoplasms: pathology /
Receptors, Chimeric Antigen: immunology / Receptors,
Chimeric Antigen: metabolism / Receptors, Chimeric Antigen:
genetics / Cell Line, Tumor / Xenograft Model Antitumor
Assays / T-Lymphocytes: immunology / T-Lymphocytes:
metabolism / Glioblastoma (Other) / immunotherapy (Other) /
mSA2 CAR-T cells (Other) / universal antigen targeting
(Other) / Receptors, Chimeric Antigen (NLM Chemicals)},
cin = {B320 / HD01 / D170 / W111 / B300},
ddc = {610},
cid = {I:(DE-He78)B320-20160331 / I:(DE-He78)HD01-20160331 /
I:(DE-He78)D170-20160331 / I:(DE-He78)W111-20160331 /
I:(DE-He78)B300-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40518621},
doi = {10.1080/2162402X.2025.2518631},
url = {https://inrepo02.dkfz.de/record/302114},
}