Antitumor immune response induced by DNA vaccine encoding human prostate-specific membrane antigen and mouse 4-1BBL.
OBJECTIVE
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.
Kuang
Youlin
Y
Department of Urology, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, China.
Zhu
Hengcheng
H
Weng
Xiaodong
X
Liu
Xiuheng
X
Chen
Zhiyuan
Z
Chen
Hui
H
Jiang
Botao
B
Zheng
Yongfa
Y
D053330:4-1BB Ligand / Q000235:genetics*; D000818:Animals; D000954:Antigens, Surface / Q000235:genetics*; D005260:Female; D043425:Glutamate Carboxypeptidase II / Q000235:genetics*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000517:prevention & control*; D019444:Vaccines, DNA
D053330:4-1BB Ligand; D000954:Antigens, Surface; D019444:Vaccines, DNA; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II