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

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Version 1 2021-12-31, 15:07
journal contribution
posted on 2024-06-19, 07:30 authored by K Singh, KM Hotchkiss, AA Mohan, JL Reedy, JH Sampson, M Khasraw
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.

History

Journal

Journal for ImmunoTherapy of Cancer

Volume

9

Article number

e003679

Pagination

1-12

Location

London, Eng.

Open access

  • Yes

ISSN

2051-1426

eISSN

2051-1426

Language

English

Publication classification

C1 Refereed article in a scholarly journal

Issue

11

Publisher

BMJ