Antitumor Immune Response Induced by DNA Vaccine Encoding Human Prostate-specific Membrane Antigen and Mouse 4-1BBL

作者：Kuang, Youlin; Zhu, Hengcheng; Weng, Xiaodong; Liu, Xiuheng^*; Chen, Zhiyuan; Chen, Hui; Jiang, Botao; Zheng, Yongfa

来源：Urology, 2010, 76(2): 510.e1.

DOI：10.1016/j.urology.2010.02.054

• T-CELLS
• MONOCLONAL-ANTIBODY
• ACID-PHOSPHATASE
• CANCER
• EXPRESSION
• GENE
• IMMUNOTHERAPY
• LYMPHOCYTES
• SURVIVAL
• TRIAL

OBJECTIVES To determine whether a novel DNA vaccine encoding truncated human prostate-specific membrane antigen (tPSMA) can be enhanced by a genetically enhanced adjuvant (4-1BB ligand [4-1BBL]).
METHODS A eukaryotic expression plasmid pDC316-tPSMA-internal ribosome entry site-mouse 4-1BBL (pDC316-tPSMA-IRES-m4-1BBL) was constructed. The efficacy of vaccination using pDC316tPSMA-IRES-m4-1BBL was compared with pDC316-tPSMA in terms of the antigen-specific cytotoxic T lymphocyte activity and antitumor immunity to RM-1-tPSMA in a murine tumor model.
RESULTS pDC316-tPSMA-IRES-m4-1BBL induced potent cytotoxicity against RM-1-tPSMA cells expressing tPSMA (42.6% specific killing) compared with pDC316-tPSMA vaccinated mice (24.8% killing) and mice not vaccinated (10.8% killing; P <.01). Moreover, the vaccination of mice with pDC316-tPSMA-IRES-m4-1BBL induced a potent protective antitumor immunity to RM-1-tPSMA in a subcutaneous tumor model.
CONCLUSIONS These results suggest that a specific antitumor immune response is enhanced by DNA vaccines expressing PSMA and 4-1BBL. This approach could offer a new strategy for treating carcinoma of the prostate after standard therapy. UROLOGY 76: 510.e1-510.e6, 2010.

• 出版日期2010-8
• 单位武汉大学