[Anti-tumor immune response of dendritic cells transfected with wild-type p53 gene].
OBJECTIVE
To explore the anti-tumor immune responses of dendritic cells (DCs) loaded with intact wild-type p53 to mice challenged with tumor cells expressing p53 genes with mutations at different sites.


METHODS
Ad-p53-DC immunization function was assessed by the expression of surface molecules and allogeneic MLR. DCs derived from bone marrow were transduced with adenovirus or a human wild-type p53 containing recombinant adenovirus (Ad-DC and Ad-p53-DC) and immunized C57BL/6 mice. Splenocytes were separated and cell cytotoxicity was measured against tumor cells expressing mutant p53 (MethA, D459 and P815) in a standard 6-h(51)Cr-release assay. Effector and target cells were incubated in the presence of anti-CD(4) or anti-CD(8) antibody. Ad-p53-DC was immunized in control Ad-DC before or after mice were challenged with either D459 tumor or with MethA sarcoma cells to observe whether immune response would provide tumor protection.


RESULTS
Immunization with Ad-p53-DC developed significantly higher substantial CTL responses against Ad-p53-P815, D459 and MethA cells (effectors: target cells = 50:1), (27.8 +/- 3.4)%, (23.5 +/- 2.7)%, (58.3 +/- 9.2)% than with Ad-DC (9.3 +/- 1.8)%, (4.6 +/- 1.0)%, (23.5 +/- 3.7)% (t(d) = 5.79, 3.68, 5.02, all P < 0.05). In Ad-p53-DC immunized mice, anti-CD(8) antibody blocked the cytotoxicity against Ad-p53-P815 (26.7 +/- 2.8)% or D459 (6.1 +/- 1.2)%, but not anti-CD(4) antibody [(59.8 +/- 4.6)%, (18.9 +/- 2.4)%, t(d) = 8.79 or 9.18, all P < 0.05]. Ad-p53-DC immunization provided complete tumor protection in 80% of mice challenged with D459 and in 70% of mice challenged with MethA, while none protected in Ad-DC immunization group (chi(2) = 6.72, 5.86, all P < 0.05). Treated with Ad-p53-DC after D459 inoculation subcutaneously, mice were killed due to the bulky tumor more than 2 weeks later than the mice in the Ad-DC treatment group during 7 week observation (chi(2) = 9.48, P < 0.05).


CONCLUSIONS
DCs transfected with 100 MOI Ad-p53 induced intense CTL responses against P815, D459 and MethA. This CTL response is mediated by CD(8)(+) T cells. Treatment with Ad-p53-DC significantly developed tumor immunology and slowed the growth of established tumors.
Liu
Hong-Ju
HJ
Department of Respiratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Xin
Jian-Bao
JB
Li
Zhuo-Ya
ZY
Xiong
Xian-Zhi
XZ
Tao
Xiao-Nan
XN
Hu
Yu
Y
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001854:Bone Marrow Cells; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D005822:Genetic Vectors; D007167:Immunotherapy; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D016159:Tumor Suppressor Protein p53