2. Academic Validation
  3. The safety and efficacy of bispecific T-cell engagers (TCEs) in patients with glioma

The safety and efficacy of bispecific T-cell engagers (TCEs) in patients with glioma

  • Clin Exp Med. 2026 Feb 14;26(1):153. doi: 10.1007/s10238-026-02057-y.
Behrouz Robat-Jazi 1,  Parsa Lorestani 2,  Negar Nejati 3,  Elaheh Ebrahimi 4,  Mohammad Amin Habibi 5,  Mahsa Ahmadpour 6,  Armita Jokar-Derisi 7,  Zahra Karimizadeh 8,  Kamyar Bagheri 9,  Sajjad Ahmadpour 10
Affiliations

Affiliations

  • 1 Research Center for Chronic Inflammatory Diseases, Tehran University of Medical Sciences, Tehran, Iran.
  • 2 Students Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran.
  • 3 Research assistant for pediatric Cell and Gene Therapy Research Centre, Gene, Cell & Tissue Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
  • 4 Patient Safety Research Center, Clinical Research Institute, Urmia University of Medical Sciences, Urmia, Iran.
  • 5 Department of Neurosurgery, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. [email protected].
  • 6 Department of Internal Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
  • 7 Student Research Committee, school of Medicine, Shiraz University of Medical sciences, Shiraz, Iran.
  • 8 Pediatric Cell and Gene Therapy Research Centre, Gene, Cell & Tissue Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
  • 9 Abadan University of Medical Sciences, Abadan, Iran.
  • 10 Patient Safety Research Center, Clinical Research Institute, Urmia University of Medical Sciences, Urmia, Iran. [email protected].
PMID: 41689667 DOI: 10.1007/s10238-026-02057-y
Abstract

Among the most aggressive and resistant tumors of the central nervous system, glioblastoma (GBM) has a poor prognosis and few available treatments. Because of the tumor's infiltrative nature, immunosuppressive environment, and resistance mechanisms, traditional treatments such as radiotherapy, chemotherapy, and surgery offer only modest survival benefits. Bispecific T-cell engagers (TCEs) have shown promising preclinical and early clinical results, and immunotherapy has become a feasible strategy. TCEs efficiently promote antigen evasion and strong tumor lysis by directing cytotoxic T lymphocytes (CTLs) to tumor-associated antigens (TAA) such as the EGFRvIII ligands IL-13Rα2, Fn14, and NKG2D ligands (NKG2DLs). Although phase I clinical studies with AMG 596 have shown acceptable safety profiles and early indications of efficacy, preclinical mice have demonstrated prolonged longevity. However, challenges still exist, including the short half-life of TCEs molecules, limited T-cell infiltration, antigen heterogeneity, and the risk of neurotoxicity or cytokine release syndrome (CRS). Promising developments include novel approaches such as multivalent targeting, DNA-encoded or cell-delivered TCEs, and combinations with immune checkpoint inhibitors (ICIs) or CAR-T cells. With an emphasis on its integration into multimodal treatment approaches, this review highlights the safety, effectiveness, and potential uses of TCEs immunotherapy for gliomas.

Keywords

Bispecific t-cell engagers; Glioblastoma; Glioma; Immunotherapy; Tumor microenvironment.

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