Chimeric Antigen Receptor-Engineered T Cell Therapy for the Management of Patients with Metastatic Prostate Cancer: A Comprehensive Review
Abstract
:1. Introduction
2. The Molecular Construct of CAR-T Cells
3. The CAR-T Cell Therapy Platform
4. The Role of Prostate Tumor Associated Antigens in CAR-T Cell Therapy
4.1. Prostate Specific Antigen
4.2. Prostate Specific Membrane Antigen
4.3. Prostate Sten Cell Antigen
4.4. Prostatic Acid Phosphatase
5. The Clinical Role of CAR-T Cell Therapy in the Setting of Metastatic PCa
5.1. PSMA CAR-T Cells
5.2. PSCA CAR-T Cells
5.3. EpCAM CAR-T Cells
6. Current Limitations of CAR-T Therapy in the PCa Treatment Setting
6.1. CAR-T Cell Persistence and Tumor Trafficking
6.2. The Prostate Cancer Tumor Microenvironment
6.3. Immune-Related Adverse Events
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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CAR-T Cell Type | CAR-T Cell Generation | Clinical Phase | Identifier or Study Title | Costimulatory Domain | Primary Endpoints |
---|---|---|---|---|---|
PSMA CAR-T | First generation | Preclinical | Targeted elimination of prostate cancer by genetically directed human T lymphocytes [54] | Tumor specificity Tumor response | |
PSMA CAR-T | Second generation | Preclinical | Human T lymphocyte cytotoxicity and proliferation directed by a single chimeric TCRζ/CD 28 receptor [55] | CD 28 | Specific tumor lysis activity |
PSMA CAR-T | Second generation | Preclinical | PSMA-specific CAR-engineered T cells eradicate disseminated prostate cancer in preclinical models [56] | CD 28 | In vivo antitumor activity |
PSMA CAR-T | Second generation | Phase I | NCT00664196 [57] | Safety partial response | |
PSMA CAR-T | Second generation | Preclinical | Advanced generation anti- prostate specific membrane antigen designer T cells for prostate cancer immunotherapy [58] | CD 28 | PSMA-specific cytotoxicity |
Autologous PSMA CAR-T | Second generation | Phase I | NCT01140373 [59] | CD 28 | Safety, tolerability |
Anti-PSMA TGF-β insensitive CAR-T | Second generation | Phase I | NCT03089203 [60] | 4-1BB | Adverse events |
Anti-PSMA TGF-β insensitive CAR-T | Second generation | Preclinical | Efficacy against human prostate cancer by prostate specific membrane antigen -specific transforming growth factor-β insensitive genetically targeted CD 8+ T cells derived from patients with Metastatic castrate-resistant disease [61] | 4-1BB | Antitumor activity |
VHH-CAR-T Anti-PSMA | Second generation | Preclinical | Construction of a chimeric antigen receptor bearing a nanobodyagainst prostate specific membrane antigen in prostate cancer [62] | CD 28 | Cytotoxicity potential |
CAR-T Cell Type | CAR-T Cell Generation | Clinical Phase | Identifier or Study Title | Costimulatory Domain | Primary Endpoints |
---|---|---|---|---|---|
PSCA CAR-T | Second generation | Preclinical | Costimulatory signaling determines tumor antigen sensitivity and persistence of CAR-T cells targeting PSCA+ metastatic prostate cancer [63] | CD 28, 4-1BB | Antitumor activity |
BPX-601 | Third generation | Phase I | NCT02744287 [64] | CD 40, MyD88 | Toxicity, adverse events |
CAR-T Cell Type | CAR-T Cell Generation | Clinical Phase | Identifier or Study Title | Costimulatory Domain | Primary Endpoints |
---|---|---|---|---|---|
EpCAM CAR-T | Second generation | Preclinical | Adoptive T cell therapy of prostate cancer targeting the cancer stem cell antigen EpCAM [68] | CD 28 | Antitumor activity |
EpCAM CAR-T | Second generation | Phase I/II | NCT03013712 [69] | CD 28, CD 3 | Toxicity Adverse events |
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Yu, Y.D.; Kim, T.J. Chimeric Antigen Receptor-Engineered T Cell Therapy for the Management of Patients with Metastatic Prostate Cancer: A Comprehensive Review. Int. J. Mol. Sci. 2021, 22, 640. https://doi.org/10.3390/ijms22020640
Yu YD, Kim TJ. Chimeric Antigen Receptor-Engineered T Cell Therapy for the Management of Patients with Metastatic Prostate Cancer: A Comprehensive Review. International Journal of Molecular Sciences. 2021; 22(2):640. https://doi.org/10.3390/ijms22020640
Chicago/Turabian StyleYu, Young Dong, and Tae Jin Kim. 2021. "Chimeric Antigen Receptor-Engineered T Cell Therapy for the Management of Patients with Metastatic Prostate Cancer: A Comprehensive Review" International Journal of Molecular Sciences 22, no. 2: 640. https://doi.org/10.3390/ijms22020640