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- Title
PSMA-Specific CAR-Engineered T Cells Eradicate Disseminated Prostate Cancer in Preclinical Models.
- Authors
Zuccolotto, Gaia; Fracasso, Giulio; Merlo, Anna; Montagner, Isabella Monia; Rondina, Maria; Bobisse, Sara; Figini, Mariangela; Cingarlini, Sara; Colombatti, Marco; Zanovello, Paola; Rosato, Antonio
- Abstract
Immunology-based interventions have been proposed as a promising curative chance to effectively attack postoperative minimal residual disease and distant metastatic localizations of prostate tumors. We developed a chimeric antigen receptor (CAR) construct targeting the human prostate-specific membrane antigen (hPSMA), based on a novel and high affinity specific mAb. As a transfer method, we employed last-generation lentiviral vectors (LV) carrying a synthetic bidirectional promoter capable of robust and coordinated expression of the CAR molecule, and a bioluminescent reporter gene to allow the tracking of transgenic T cells after in vivo adoptive transfer. Overall, we demonstrated that CAR-expressing LV efficiently transduced short-term activated PBMC, which in turn were readily stimulated to produce cytokines and to exert a relevant cytotoxic activity by engagement with PSMA+ prostate tumor cells. Upon in vivo transfer in tumor-bearing mice, CAR-transduced T cells were capable to completely eradicate a disseminated neoplasia in the majority of treated animals, thus supporting the translation of such approach in the clinical setting.
- Subjects
PROSTATE tumors; ANTIGENS; CYTOTOXIC T cells; TRANSGENIC animals; ANIMAL models in research
- Publication
PLoS ONE, 2014, Vol 9, Issue 10, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0109427