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Updated: Apr 23, 2026
Generation of Prostate Cancer Patient Derived Xenograft Models from Circulating Tumor Cells
Published on: October 20, 2015
PSMA-specific CAR-engineered T cells eradicate disseminated prostate cancer in preclinical models
Gaia Zuccolotto1, Giulio Fracasso2, Anna Merlo3
1Department of Medicine, University of Padua, Padua, Italy.
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.
Insights
Chimeric antigen receptor (CAR) T-cell therapy targeting prostate-specific membrane antigen (hPSMA) shows promise for treating prostate cancer. This novel immunotherapy eradicated disseminated tumors in mice, supporting clinical translation.
Area of Science:
- Immunology
- Oncology
- Gene Therapy
Background:
- Minimal residual disease and metastasis in prostate cancer pose significant challenges.
- Immunotherapy offers a potential strategy to target residual and metastatic prostate tumors.
Purpose of the Study:
- To develop and evaluate a chimeric antigen receptor (CAR) T-cell therapy targeting the human prostate-specific membrane antigen (hPSMA).
- To assess the efficacy of CAR T-cells in eradicating disseminated prostate tumors in a preclinical model.
Main Methods:
- Development of a novel CAR construct targeting hPSMA using a high-affinity monoclonal antibody (mAb).
- Utilized lentiviral vectors (LV) with a synthetic bidirectional promoter for CAR and reporter gene expression.
- Transduction of peripheral blood mononuclear cells (PBMCs) and assessment of their cytotoxic activity and cytokine production.
- In vivo adoptive transfer of CAR-transduced T-cells in tumor-bearing mice.
Main Results:
- LV efficiently transduced activated PBMCs, leading to robust CAR expression.
- CAR T-cells demonstrated cytokine production and cytotoxic activity against PSMA+ prostate tumor cells.
- Complete eradication of disseminated tumors was achieved in a majority of treated mice.
Conclusions:
- CAR T-cell therapy targeting hPSMA is a potent strategy against prostate cancer.
- The developed LV-based CAR construct shows significant potential for clinical application in treating prostate cancer.
- This approach may effectively address minimal residual disease and metastatic prostate tumors.
