Effects of dendritic cells transfected with full length wild-type p53 and modified by bile duct cancer lysates on immune response.
BACKGROUND
Dendritic cells (DCs) are the most potent antigen-presenting cells and are actively used in cancer immunotherapy. Wild-type p53 can be recognized as an antigen and can induce specific cytotoxic T lymphocytes (CTLs) in the host body. The aim of this study was to investigate the effects of DCs transfected with full length wild-type p53 and modified by bile duct lysates on immune response.


METHODS
The wild-type p53 was transducted to DCs with adenovirus, which were modified by bile duct lysates (Lywtp53DC). The concentration of the surface molecules (B7-1, B7-2, MHC-I, MHC-II) of all DCs was detected with fluorescence activated cell sorter (FACS), and the ability of the DCs to induce efficient and specific immunological response in anti-(51)Cr-labeled target cells was studied. BALB/c mice infected with the DCs and QBC939 were used. CTL response in mice immunized with Lywtp53DC and treatment of tumor-bearing mice with Lywtp53DC and CTL response in these mice were studied.


RESULTS
The surface molecules of Lywtp53DC had a high expression B7-1 (86.70%+/-0.07%), B7-2 (18.77%+/-0.08%), MHC-I(87.20%+/-0.05%), MHC-II(56.70%+/-0.07%) with FACS. The T lymphocytes had a specific CTL lysing ability induced by Lywtp53DC, with a CTL lysis rate of 81%. The immune protection of Lywtp53DC group was obvious, and the tumor diameter of the Lywtp53DC group was 3.10+/-0.31 mm, 2.73+/-0.23 mm, 3.70+/-0.07 mm on days 13, 16 and 19, smaller than those of any control groups (P<0.05), DC, wtp53DC and LyDC. On the other hand, the growth rate of tumor of the Lywtp53DC group was slower than that of any other groups (P<0.05).


CONCLUSIONS
Dendritic cells transfected with wild-type p53 and modified by bile duct lysates have specific CTL killing capability.
Sun
Hua-Wen
HW
Department of General Surgery, Renmin Hospital, Wuhan University, Wuhan 430060, China. sxshwyq@sina.com
Tang
Qi-Bing
QB
Tang
Chong
C
Zou
Sheng-Quan
SQ
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001650:Bile Duct Neoplasms / Q000276:immunology* / Q000628:therapy*; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D016158:Genes, p53; D016219:Immunotherapy, Adoptive; D051379:Mice; D008807:Mice, Inbred BALB C; D012680:Sensitivity and Specificity; D014020:Tissue Extracts / Q000276:immunology; D014162:Transfection; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000276:immunology*
D014020:Tissue Extracts; D016159:Tumor Suppressor Protein p53