Fully Humanized Bispecific T Cell Engager Shows Potent Activity in Central Nervous System and Peripheral Tumors.
Overview
- Department of Neurological Surgery, Northwestern University, Chicago, IL, USA
- Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
- Department of Pathology, Northwestern University, Chicago, IL, USA
- Feinberg Cardiovascular and Renal Research Institute, Northwestern University, Chicago, IL, USA
- Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Department of Laboratory Medicine & Pathology, Mayo Clinic Florida, Jacksonville, FL, USA
- Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO, USA
- Colorado Center for Nanomedicine and Nanosafety, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
Abstract
Bispecific T cell engagers (BTEs) induce MHC‐independent cytotoxicity by bridging T cells to tumor cells via binding a T cell–activating receptor and a tumor‐associated antigen. BTEs have proven effective in hematologic malignancies and some solid tumors, yet their potential in glioblastoma (GBM) is largely unexplored. We developed a fully humanized BTE (hBTE) targeting interleukin‐13 receptor alpha 2 (IL13RA2), a tumor‐associated antigen widely expressed in GBM and associated with poor prognosis. In vitro, hBTE activated T cells and induced antigen‐dependent cytokine release and cytotoxicity against IL13RA2‐positive GBM cells. In vivo, hBTE showed robust target‐specific activity and markedly prolonged survival in primary and recurrent GBM xenograft models, without detectable off‐target local or systemic toxicity. Beyond GBM, hBTE also exhibited antitumor activity in IL13RA2‐expressing solid tumors, demonstrating selective tumor accumulation and therapeutic efficacy in models of breast cancer brain metastases and extracranial lung cancer. This work highlights the therapeutic potential of BTEs in IL13RA2‐expressing tumors and establishes a strong preclinical rationale for advancing hBTE therapy toward clinical translation in GBM and other tumors.
Reproduced under the paper's license (CC BY), from the paper cited above.
Code
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Data
Data links
- ncbi.nlm.nih.gov/
geo/ , NCBI; found in “Analysis of Publicly Available RNA Sequencing…”query
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.
Version 1, 30 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 17 authors, 7 keywords, 13 MeSH terms, 5 funders, 76 references, 3 RRIDs.
Cite
This paper
Duffy, J. T., Martin‐Regalado, A., Haupt, B. E., Pogue, J. R., Thakur, A., Cota, M. F., Zannikou, M., Misener, S., Krymskaya, V. P., McCortney, K., Miska, J., Horbinski, C., Simberg, D., Lesniak, M. S., James, C. D., Stupp, R., & Balyasnikova, I. V. (2026). Fully Humanized Bispecific T Cell Engager Shows Potent Activity in Central Nervous System and Peripheral Tumors. Advanced science (Weinheim, Baden-Wurttemberg, Germany), 13(35), e22391. https://
BibTeX
@article{duffy2026fully,
author = {Duffy, Joseph T and Martin‐Regalado, Angela and Haupt, Benedikt E and Pogue, Jacob R and Thakur, Aditi and Cota, Manuel Fierro and Zannikou, Markella and Misener, Sol and Krymskaya, Vera P and McCortney, Kathleen and Miska, Jason and Horbinski, Craig and Simberg, Dmitri and Lesniak, Maciej S and James, Charles D and Stupp, Roger and Balyasnikova, Irina V},
title = {{Fully Humanized Bispecific T Cell Engager Shows Potent Activity in Central Nervous System and Peripheral Tumors}},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
year = {2026},
month = apr,
volume = {13},
number = {35},
pages = {e22391},
publisher = {Wiley},
issn = {2198-3844},
doi = {10.1002/
url = {https://
pmid = {42057694},
pmcid = {PMC13292153}
}
RIS
TY - JOUR
AU - Duffy, Joseph T
AU - Martin‐Regalado, Angela
AU - Haupt, Benedikt E
AU - Pogue, Jacob R
AU - Thakur, Aditi
AU - Cota, Manuel Fierro
AU - Zannikou, Markella
AU - Misener, Sol
AU - Krymskaya, Vera P
AU - McCortney, Kathleen
AU - Miska, Jason
AU - Horbinski, Craig
AU - Simberg, Dmitri
AU - Lesniak, Maciej S
AU - James, Charles D
AU - Stupp, Roger
AU - Balyasnikova, Irina V
TI - Fully Humanized Bispecific T Cell Engager Shows Potent Activity in Central Nervous System and Peripheral Tumors
T2 - Advanced science (Weinheim, Baden-Wurttemberg, Germany)
J2 - Adv Sci (Weinh)
PY - 2026
DA - 2026/
VL - 13
IS - 35
SP - e22391
SN - 2198-3844
PB - Wiley
DO - 10.1002/
UR - https://
LA - en
ER -
CSL-JSON
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