Clinical-scale manufacturing of CD137+ enriched tumor-reactive T cells for glioblastoma in the CliniMACS Prodigy
9 affiliations
- 1Miltenyi Biotec GmbH, Bergisch Gladbach, Germany
- 2Division of Clinical Neurooncology, University Hospital of Essen, Essen, Germany
- 3Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Hospital of Essen, Essen, Germany
- 4Department of Neurosurgery and Spine Surgery, Center for Translational Neuro- and Behavioural Sciences (C-TNBS), University Hospital of Essen, Essen, Germany
- 5Department of Neurology and Neurooncology, St. Marien Hospital, Lünen, Germany
- 6Department of Neurooncology, Center for Neurology, University Hospital Bonn, Bonn, Germany
- 7Department of Neurosurgery, University Hospital Bonn, Bonn, Germany
- 8Department of Neurosurgery, University Hospital Frankfurt, Frankfurt, Germany
- 9Department of Surgery, Institute of Clinical Sciences, University of, Gothenburg, Sweden
Abstract
Background: Most tumor-infiltrating lymphocyte (TIL) studies and therapies have focused on tumors with high T-cell infiltration and mutational burden. Glioblastoma (GBM) represents a challenging indication for TIL therapy because of its limited T-cell infiltration and low mutational burden. We investigated whether targeted enrichment of tumor-reactive T cells using CD137-based selection could enable robust, clinical-scale production of TIL products from GBM.
Methods: Ultrasonic aspirates (UAs), routinely collected during GBM resections, were evaluated as a source of TILs for clinical manufacturing. TILs were generated from GBM UAs under GMP-like conditions at clinical scale using the closed, automated TRT Process on the CliniMACS Prodigy. Matched TRT products that were enriched for CD137+ cells, depleted of CD137+ cells, or left unselected were generated in parallel at full manufacturing scale. Products were characterized by cellular and transcriptomic analyses and evaluated in functional assays for cytotoxicity against autologous and non-autologous patient-derived GBM cell lines.
Results: Cellular and transcriptomic analyses revealed that UA-derived CD137+ (4-1BB/TNFRSF9) T cells were clonally expanded, exhibited activated and memory phenotypes, and displayed transcriptional profiles associated with tumor reactivity. The closed manufacturing process preserved phenotypic features previously associated with clinical benefit in other TIL indications. Functional assays demonstrated potent, tumor-reactive cytotoxicity of CD137-enriched TRT products against autologous GBM cell lines compared with TILs generated in parallel without selection.
Discussion/Conclusions: These findings establish the feasibility of a clinical-scale TIL manufacturing approach using the CliniMACS Prodigy that enables production of clinically relevant quantities of TILs from GBM while enriching for cells with tumor-reactive characteristics. This approach may broaden the application of TIL therapy to immunologically cold tumors with limited T-cell infiltration or low mutational burden that have historically been challenging to manufacture using conventional TIL production methods.
Related
- CD4 + T cells reactive to Epstein-Barr virus late lytic antigens are enriched in individuals with multiple sclerosis
- Pericyte-derived cancer-associated fibroblasts correlate with poor survival and are enriched after chemoradiotherapy in glioblastoma
- Tissue-reactive zonation of mesenchymal-like phenotypes in human glioblastoma
- A logistic paradigm to predict molecular glioblastoma on clinical MRI
- 197 Chimeric antigen receptor T-cell therapy in glioblastoma: a systematic review and meta analysis of early phase clinical trials with GRADE assessment
BibTeX
@article{riabinska2026clinicalscale,
title = {{Clinical-scale manufacturing of CD137+ enriched tumor-reactive T cells for glioblastoma in the CliniMACS Prodigy}},
author = {Arina Riabinska and Elvira Criado-Moronati and Emre Balta and Denis Frison and Cristina Berganza-Irusqueta and Tümay Telatar and Donata Maciaczyk and Johanna Engeln and Laura Fischer and Marieke Domdey and Imran Siddiqui and Velita Miranda and Teresa Schmidt and Sied Kebir and Yahya Ahmadipour and Martin Glas and Ulrich Herrlinger and Matthias Schneider and Anna-Laura Potthoff and Marcus Czabanka and Thomas Broggini and Sofia Stenqvist and Lisa M. Nilsson and Jonas A. Nilsson and Martina Ott and Andrzej Dzionek and Ian R. Hardy},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1866645},
url = {https://doi.org/10.3389/fimmu.2026.1866645},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Clinical-scale manufacturing of CD137+ enriched tumor-reactive T cells for glioblastoma in the CliniMACS Prodigy
AU - Arina Riabinska
AU - Elvira Criado-Moronati
AU - Emre Balta
AU - Denis Frison
AU - Cristina Berganza-Irusqueta
AU - Tümay Telatar
AU - Donata Maciaczyk
AU - Johanna Engeln
AU - Laura Fischer
AU - Marieke Domdey
AU - Imran Siddiqui
AU - Velita Miranda
AU - Teresa Schmidt
AU - Sied Kebir
AU - Yahya Ahmadipour
AU - Martin Glas
AU - Ulrich Herrlinger
AU - Matthias Schneider
AU - Anna-Laura Potthoff
AU - Marcus Czabanka
AU - Thomas Broggini
AU - Sofia Stenqvist
AU - Lisa M. Nilsson
AU - Jonas A. Nilsson
AU - Martina Ott
AU - Andrzej Dzionek
AU - Ian R. Hardy
PY - 2026
DA - 2026/10/12
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1866645
UR - https://doi.org/10.3389/fimmu.2026.1866645
AB - Background: Most tumor-infiltrating lymphocyte (TIL) studies and therapies have focused on tumors with high T-cell infiltration and mutational burden. Glioblastoma (GBM) represents a challenging indication for TIL therapy because of its limited T-cell infiltration and low mutational burden. We investigated whether targeted enrichment of tumor-reactive T cells using CD137-based selection could enable robust, clinical-scale production of TIL products from GBM. Methods: Ultrasonic aspirates (UAs), routinely collected during GBM resections, were evaluated as a source of TILs for clinical manufacturing. TILs were generated from GBM UAs under GMP-like conditions at clinical scale using the closed, automated TRT Process on the CliniMACS Prodigy. Matched TRT products that were enriched for CD137+ cells, depleted of CD137+ cells, or left unselected were generated in parallel at full manufacturing scale. Products were characterized by cellular and transcriptomic analyses and evaluated in functional assays for cytotoxicity against autologous and non-autologous patient-derived GBM cell lines. Results: Cellular and transcriptomic analyses revealed that UA-derived CD137+ (4-1BB/TNFRSF9) T cells were clonally expanded, exhibited activated and memory phenotypes, and displayed transcriptional profiles associated with tumor reactivity. The closed manufacturing process preserved phenotypic features previously associated with clinical benefit in other TIL indications. Functional assays demonstrated potent, tumor-reactive cytotoxicity of CD137-enriched TRT products against autologous GBM cell lines compared with TILs generated in parallel without selection. Discussion/Conclusions: These findings establish the feasibility of a clinical-scale TIL manufacturing approach using the CliniMACS Prodigy that enables production of clinically relevant quantities of TILs from GBM while enriching for cells with tumor-reactive characteristics. This approach may broaden the application of TIL therapy to immunologically cold tumors with limited T-cell infiltration or low mutational burden that have historically been challenging to manufacture using conventional TIL production methods.
SN - 1664-3224
ER -