Dendritic cells transduced with a PSMA-encoding adenovirus and cocultured with autologous cytokine-induced lymphocytes induce a specific and strong immune response against prostate cancer cells.
OBJECTIVE
The lack of curative therapies for advanced prostate cancer (PCa) has prompted a search for novel treatments such as immunotherapy. In this study, we analyzed whether dendritic cells (DCs) from healthy donors transduced with a PSMA-encoding adenovirus (Ad-PSMA) and cocultured with autologous cytokine-induced killer cells (CIKs) can induce a strong specific immune response against PCa cells in vitro.


METHODS
Ad-PSMA was constructed by DNA recombination. DCs and CIKs were prepared by cytokines induction from peripheral blood mononuclear cells, and flow cytometry was used to measure the phenotypes of DCs and CIKs. DCs were transduced with Ad-PSMA and then cocultured with autologous CIKs. The cytotoxicity of the cocultured cells against specific target LNCaP cells and control targets DU145 and PC3 cells was analyzed by a 4-h LDH release assay.


RESULTS
DCs were transduced with Ad-PSMA with transfection efficiency of 70% and the transduction did not alter typical morphology of mature DCs. The PSMA protein was effectively expressed in DCs, which were transfected with Ad-PSMA. Ad-PSMA-transduced DCs stimulated CIKs strongly to lyse about 75% of PSMA-expressing PCa cells. Furthermore, the cocultivation of Ad-PSMA-transduced DCs with CIKs could significantly increase the production of interferon-gamma after restimulated with PSMA peptide mixtures.


CONCLUSIONS
The data demonstrate that DCs, which were transduced with a PSMA-expressing adenovirus and cocultured with autologous CIKs, induce a PSMA-specific, strong immune response against PCa cells. Therefore, this approach may have a potential for an adoptive immunotherapy for patients with advanced PCa.
Wang
Kebing
K
Department of Urology, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
Gao
Xin
X
Pang
Jun
J
Liu
Xiaopeng
X
Cai
Yubin
Y
Zhang
Yan
Y
Zhou
Jianhua
J
Zhan
Hailun
H
D000256:Adenoviridae / Q000235:genetics*; D000954:Antigens, Surface / Q000378:metabolism*; D018929:Cell Culture Techniques; D002462:Cell Membrane / Q000378:metabolism; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism*; D000939:Epitopes / Q000737:chemistry; D043425:Glutamate Carboxypeptidase II / Q000378:metabolism*; D006801:Humans; D007107:Immune System; D007167:Immunotherapy / Q000379:methods*; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D010957:Plasmids / Q000378:metabolism
D000954:Antigens, Surface; D016207:Cytokines; D000939:Epitopes; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II