Anti-tumor immune response induced by dendritic cells transduced with truncated PSMA IRES 4-1 BBL recombinant adenoviruses

作者：Kuang Youlin; Weng Xiaodong; Liu Xiuheng^*; Zhu Hengchen; Chen Zhiyuan; Jiang Botao; Chen Hui

来源：Cancer Letters, 2010, 293(2): 254-262.

DOI：10.1016/j.canlet.2010.01.011

• Recombinant adenovirus
• Dendritic cells
• Prostate cancer
• 4-1BBL
• Costimulatory molecule
• Cancer immunotherapy

Up-regulation of receptor-ligand pairs during interaction of a peptide-bound MHC complex on dendritic cells (DCs) with cognate TCR may amplify, sustain, and drive diversity in the ensuing T cell immune response. Members of the TNF ligand superfamily and the TNFR superfamily contribute to this costimulatory molecule signaling. In the present study, we used replication deficient adenoviruses to introduce a tumor-associated Ag (a truncated human prostate-specific membrane antigen (tPSMA)) and the T cell costimulatory molecule 4-1BBL into murine DCs, and observed the ability of these recombinant DCs to elicit tPSMA-directed T-cell responses in vitro and anti-tumor immunity to RM-1-tPSMA in a murine tumor model. Infection of DCs with Ad-tPSMA-1RES-m4-1 BBL induced tPSMA-specific proliferative responses and up-regulated CD80 and CD86 s signaling molecules. The cytotoxic T lymphocytes activated by the Ad-tPSMA-IRES-m4-1BBL-transfected DCs showed significantly higher IFN-gamma production and cytotoxicity against the RM-1 cells transfected with tPSMA. Moreover, vaccination of mice with Ad-tPSMA-IRES-m4-1 BBL-transfected DCs induced a potent protective and therapeutic anti-tumor immunity to RM-1-tPSMA in a tumor model. These results demonstrated that development of DCs engineered to express tPSMA and 4-1BBL by recombinant adenovirus-mediated gene transfer may offer a new strategy for prostate cancer immunotherapy.

• 出版日期2010-7-28
• 单位武汉大学