Glioblastoma multiforme (GBM) is the deadliest human brain tumor with a median survival following diagnosis of 14–16 months. Innovative therapeutic approaches are urgently needed. Cancer stem cells (CSC) from GBM resist current chemo- and radio therapies and can generate recurrent and aggressive tumors. To envisage innovative therapeutic approaches of potential clinical use, we engineered T cells with Fcγ-chimeric receptors (CRs) to elicit antibody-dependent cellular cytotoxicity (ADCC) in the presence of mAbs specific for tumor associated antigens (TAA). Indeed, in previous studies, we success fully redirected CD16158V-CR T cells against KRAS-mutated colorectal carcinoma cells. Since surface overexpression of epidermal growth factor receptor (EGFR) is frequently detectable in GBM, we assessed, in vitro, the anti-GBM potential of polymorphic CD16-CR T cells, in combination with anti-EGFR mAbs, on GBM-derived EGFR+ CSC. Our results indicate that CD16158V, but not CD16158F-CR engineered T cells in cubated with cetuximab, but not panitumumab, induced the elimination of GBM-derived CSC through a caspase-3 dependent mechanism, and produced high amounts of TNFα and IFNγ upon recognition of target cells. These data pave the way towards pre-clinical development of innovative GBM treatments, taking advantage of CD16158V-CR engineered T cells and therapeutic antibodies

Cenciarelli, C., Caratelli, S., Arriga, R., Lanzilli, G., Stabile, S., Ottaviani, A., et al. (2021). EGFR+ Glioblastoma stem cells targeting by CD16158V-chimeric receptor T cells and cetuximab. ANNALS OF RESEARCH IN ONCOLOGY, 1(1), 24-35 [10.48286/aro.2021.04].

EGFR+ Glioblastoma stem cells targeting by CD16158V-chimeric receptor T cells and cetuximab

Caratelli, S.;Arriga, R.;Ottaviani, A.;Venditti, A.;Iezzi, G.;Roselli, M.;Lauro, D.;
2021-01-01

Abstract

Glioblastoma multiforme (GBM) is the deadliest human brain tumor with a median survival following diagnosis of 14–16 months. Innovative therapeutic approaches are urgently needed. Cancer stem cells (CSC) from GBM resist current chemo- and radio therapies and can generate recurrent and aggressive tumors. To envisage innovative therapeutic approaches of potential clinical use, we engineered T cells with Fcγ-chimeric receptors (CRs) to elicit antibody-dependent cellular cytotoxicity (ADCC) in the presence of mAbs specific for tumor associated antigens (TAA). Indeed, in previous studies, we success fully redirected CD16158V-CR T cells against KRAS-mutated colorectal carcinoma cells. Since surface overexpression of epidermal growth factor receptor (EGFR) is frequently detectable in GBM, we assessed, in vitro, the anti-GBM potential of polymorphic CD16-CR T cells, in combination with anti-EGFR mAbs, on GBM-derived EGFR+ CSC. Our results indicate that CD16158V, but not CD16158F-CR engineered T cells in cubated with cetuximab, but not panitumumab, induced the elimination of GBM-derived CSC through a caspase-3 dependent mechanism, and produced high amounts of TNFα and IFNγ upon recognition of target cells. These data pave the way towards pre-clinical development of innovative GBM treatments, taking advantage of CD16158V-CR engineered T cells and therapeutic antibodies
2021
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/15
English
Senza Impact Factor ISI
CD16-chimeric receptors; ADCC; cetuximab; panitumumab; EGFR; glioblastoma; cancer stem cells
Cenciarelli, C., Caratelli, S., Arriga, R., Lanzilli, G., Stabile, S., Ottaviani, A., et al. (2021). EGFR+ Glioblastoma stem cells targeting by CD16158V-chimeric receptor T cells and cetuximab. ANNALS OF RESEARCH IN ONCOLOGY, 1(1), 24-35 [10.48286/aro.2021.04].
Cenciarelli, C; Caratelli, S; Arriga, R; Lanzilli, G; Stabile, S; Ottaviani, A; Sconocchia, T; Spagnoli, Gc; Venditti, A; Iezzi, G; Roselli, M; Lauro,...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/345985
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