EphA3 CAR T cells are effective against glioblastoma in preclinical models.
J Immunother Cancer
; 12(8)2024 Aug 07.
Article
in En
| MEDLINE
| ID: mdl-39111832
ABSTRACT
BACKGROUND:
Adoptive T-cell therapy targeting antigens expressed in glioblastoma has emerged as a potential therapeutic strategy to prevent or delay recurrence and prolong overall survival in this aggressive disease setting. Ephrin receptor A3 (EphA3), which is highly expressed in glioblastoma; in particular, on the tumor vasculature and brain cancer stem cells, is an ideal target for immune-based therapies.METHODS:
We have designed an EphA3-targeted chimeric antigen receptor (CAR) using the single chain variable fragment of a novel monoclonal antibody, and assessed its therapeutic potential against EphA3-expressing patient-derived glioblastoma neurospheres, organoids and xenografted glioblastoma tumors in immunodeficient mice.RESULTS:
In vitro expanded EphA3 CAR T cells from healthy individuals efficiently recognize and kill EphA3-positive glioblastoma cells in vitro. Furthermore, these effector cells demonstrated curative efficacy in an orthotopic xenograft model of glioblastoma. EphA3 CAR T cells were equally effective in targeting patient-derived neurospheres and infiltrate, disaggregate, and induce apoptosis in glioblastoma-derived organoids.CONCLUSIONS:
This study provides compelling evidence supporting the therapeutic potential of EphA3 CAR T-cell therapy against glioblastoma by targeting EphA3 associated with brain cancer stem cells and the tumor vasculature. The ability to target patient-derived glioblastoma underscores the translational significance of this EphA3 CAR T-cell therapy in the pursuit of effective and targeted glioblastoma treatment strategies.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Glioblastoma
/
Receptor, EphA3
Limits:
Animals
/
Humans
Language:
En
Journal:
J Immunother Cancer
Year:
2024
Document type:
Article
Country of publication: