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PSMA-Specific CAR-Engineered T Cells Eradicate Disseminated Prostate Cancer in Preclinical Models.(Research Article)

Zuccolotto, Gaia ; Fracasso, Giulio ; Merlo, Anna ; Montagner, Isabella Monia ; Rondina, Maria ; Bobisse, Sara ; Figini, Mariangela ; Cingarlini, Sara ; Colombatti, Marco ; Zanovello, Paola ; Rosato, Antonio

PLoS ONE, Oct 3, 2014, Vol.9(10) [Peer Reviewed Journal]

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  • Title:
    PSMA-Specific CAR-Engineered T Cells Eradicate Disseminated Prostate Cancer in Preclinical Models.(Research Article)
  • Author: Zuccolotto, Gaia ; Fracasso, Giulio ; Merlo, Anna ; Montagner, Isabella Monia ; Rondina, Maria ; Bobisse, Sara ; Figini, Mariangela ; Cingarlini, Sara ; Colombatti, Marco ; Zanovello, Paola ; Rosato, Antonio
  • Subjects: T Cells ; B Cells ; Prostate Cancer ; Genetic Engineering
  • Is Part Of: PLoS ONE, Oct 3, 2014, Vol.9(10)
  • Description: 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.sup.+ 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.
  • Language: English
  • Identifier: ISSN: 1932-6203
  • Source: Cengage Learning, Inc.

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