Antitumor immune response induced by DNA vaccine encoding human prostate-specific membrane antigen and mouse 4-1BBL.

摘要

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 pDC316-tPSMA-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.