HER2 chimeric antigen receptor T cell immunotherapy is an effective treatment for diffuse intrinsic pontine glioma
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Date
2023
Authors
Wang, S.S.
Davenport, A.J.
Iliopoulos, M.
Hughes-Parry, H.E.
Watson, K.A.
Arcucci, V.
Mulazzani, M.
Eisenstat, D.D.
Hansford, J.R.
Cross, R.S.
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Journal article
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Neuro-Oncology Advances, 2023; 5(1):1-13
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Stacie S. Wang, Alexander J. Davenport, Melinda Iliopoulos, Hannah E. Hughes-Parry, Katherine A. Watson, Valeria Arcucci, Matthias Mulazzani, David D. Eisenstat, Jordan R. Hansford, Ryan S. Cross, and Misty R. Jenkins
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Abstract
Background: Diffuse intrinsic pontine glioma (DIPG) and other diffuse midline gliomas (DMG) of the thalamus and spinal cord are rare but devastating high-grade glial tumors of childhood with no curative treatment. Despite aggressive treatment attempts the prognosis has remained poor. Chimeric antigen receptor (CAR) T cell therapy has been identified as a promising new approach in the treatment of DMG tumors; however, additional targets are urgently required given known tumor heterogeneity and the prospect of antigen escape of this cancer. Methods: Using cell surface mass spectrometry, we detected high HER2 cell surface protein across a panel of patient-derived DIPG cells, thereby identifying an existing CAR T cell therapy for use in DIPG. Primary human T cells were transduced to express a second-generation HER2 CAR and interrogated for efficacy against patient-derived DIPG cells. Results: HER2 CAR T cells demonstrated potent and antigen-specific cytotoxicity and cytokine secretion when co-cultured with patient-derived DIPG cells. Furthermore, HER2 CAR T cells provided a significant regression in intracranial DIPG xenograft tumors. Conclusions: HER2 CAR T cells are already in clinic development and are well tolerated in pediatric patients. Here we provide strong preclinical evidence for the inclusion of DIPG patients in future pediatric CNS tumor HER2 CAR T cell clinical trials.
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Advance Access date 4 May 2023
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© The Author(s) 2023. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https:// creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.