Journal
CANCER RESEARCH
Volume 78, Issue 12, Pages 3337-3349Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-17-3140
Keywords
-
Categories
Funding
- Italian Ministry of Health [RF-2010-2316606, GR-2013-02359212]
- AIRC (Associazione Italiana Ricerca sul Cancro) [9962]
- Ricerca Corrente
- Fondazione Neuroblastoma
- Istituto Giuseppe Toniolo di Studi Superiori
- Associazione Heal onlus
Ask authors/readers for more resources
Medulloblastoma is the most frequent malignant childhood brain tumor with a high morbidity. identification of new therapeutic targets would be instrumental in improving patient outcomes. We evaluated the expression of the tumor-associated antigen PRAME in biopsies from 60 patients with medulloblastoma. PRAME expression was detectable in 82% of tissues independent of molecular and histopathologic subgroups. High PRAME, expression also correlated with worse overall survival. We next investigated the relevance of PRAME as a target for immunotherapy. Medulloblastoma cells were targeted using genetically modified T cells with a PRAME-specific TCR (SLL TCR T cells). SLL TCR E cells efficiently killed medulloblastoma HLA-A*02(+) DAM cells as well as primary HIA-A*02(+) medulloblastoma cells. Moreover, SLL TCR T-cells controlled tumor growth in an orthotopic mouse model of medulloblastoma. To prevent unexpected T-cell- related toxicity, an inducible caspase-9 (iC9) gene was introduced in frame with the SLL TCR; this safety switch triggered prompt elimination of genetically modified T cells. Altogether, these data indicate that T cells genetically modified with a high-affinity, PRAME-specific TCR and iC9 may represent a promising innovative approach for treating patients with HLA-A*02(+) medulloblastoma. Significance: These findings identify PRAME as a medulloblastoma tumor-associated antigen that can he targeted using genetically modified T cells. 49. (C) 2018 AACR.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available