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For whom the T cells troll? Bispecific T-cell engagers in glioblastoma.

Publication ,  Journal Article
Singh, K; Hotchkiss, KM; Mohan, AA; Reedy, JL; Sampson, JH; Khasraw, M
Published in: J Immunother Cancer
November 2021

Glioblastoma is the the most common primary brain tumor in adults. Onset of disease is followed by a uniformly lethal prognosis and dismal overall survival. While immunotherapies have revolutionized treatment in other difficult-to-treat cancers, these have failed to demonstrate significant clinical benefit in patients with glioblastoma. Obstacles to success include the heterogeneous tumor microenvironment (TME), the immune-privileged intracranial space, the blood-brain barrier (BBB) and local and systemic immunosuppressions. Monoclonal antibody-based therapies have failed at least in part due to their inability to access the intracranial compartment. Bispecific T-cell engagers are promising antibody fragment-based therapies which can bring T cells close to their target and capture them with a high binding affinity. They can redirect the entire repertoire of T cells against tumor, independent of T-cell receptor specificity. However, the multiple challenges posed by the TME, immune privilege and the BBB suggest that a single agent approach may be insufficient to yield durable, long-lasting antitumor efficacy. In this review, we discuss the mechanism of action of T-cell engagers, their preclinical and clinical developments to date. We also draw comparisons with other classes of multispecific antibodies and potential combinations using these antibody fragment therapies.

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Published In

J Immunother Cancer

DOI

EISSN

2051-1426

Publication Date

November 2021

Volume

9

Issue

11

Location

England

Related Subject Headings

  • T-Lymphocytes
  • Humans
  • Glioblastoma
  • Brain Neoplasms
  • Antibodies, Bispecific
  • 3211 Oncology and carcinogenesis
  • 3204 Immunology
 

Citation

APA
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MLA
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Singh, K., Hotchkiss, K. M., Mohan, A. A., Reedy, J. L., Sampson, J. H., & Khasraw, M. (2021). For whom the T cells troll? Bispecific T-cell engagers in glioblastoma. J Immunother Cancer, 9(11). https://doi.org/10.1136/jitc-2021-003679
Singh, Kirit, Kelly M. Hotchkiss, Aditya A. Mohan, Jessica L. Reedy, John H. Sampson, and Mustafa Khasraw. “For whom the T cells troll? Bispecific T-cell engagers in glioblastoma.J Immunother Cancer 9, no. 11 (November 2021). https://doi.org/10.1136/jitc-2021-003679.
Singh K, Hotchkiss KM, Mohan AA, Reedy JL, Sampson JH, Khasraw M. For whom the T cells troll? Bispecific T-cell engagers in glioblastoma. J Immunother Cancer. 2021 Nov;9(11).
Singh, Kirit, et al. “For whom the T cells troll? Bispecific T-cell engagers in glioblastoma.J Immunother Cancer, vol. 9, no. 11, Nov. 2021. Pubmed, doi:10.1136/jitc-2021-003679.
Singh K, Hotchkiss KM, Mohan AA, Reedy JL, Sampson JH, Khasraw M. For whom the T cells troll? Bispecific T-cell engagers in glioblastoma. J Immunother Cancer. 2021 Nov;9(11).
Journal cover image

Published In

J Immunother Cancer

DOI

EISSN

2051-1426

Publication Date

November 2021

Volume

9

Issue

11

Location

England

Related Subject Headings

  • T-Lymphocytes
  • Humans
  • Glioblastoma
  • Brain Neoplasms
  • Antibodies, Bispecific
  • 3211 Oncology and carcinogenesis
  • 3204 Immunology