[Experimental study of the specific immunoresponse induced by p53 modified dendritic cells].

Objective: To explore the specific cytotoxic T lymphocyte (CTL) induced by dendritic cells (DC), which were transfected by the plasmid pC53-SN3 encoding p53 gene.

Methods: DC derived from HLA-A2(+) mononuclear cells of the 24-lung cancer patients was transfected with the plasmid pC53-SN3 by lipofectamine and then co-cultured with auto-unpurified T cells to induce potent CTL (T-pC53-SN3). The cytolysis of specific CTL against Calu-6, a HLA-A2(+) human lung cancer cell line, was measured by using lactate dehydrogenase (LDH) releasing assay.

Results: The expression of CD(1a) and CD(83), the correlative markers of DC, increased apparently after transfected with plasmid pC53-SN3, the expression rate was (5.45 +/- 0.89)% and (3.26 +/- 0.47)% versus (52.15 +/- 11.56)% and (25.78 +/- 12.35)%. CD(14) decreased apparently, but other DC correlative markers of CD(1a), CD(40), CD(86), and HLA-DR remained almost the same as that before transfection. Compared with T-IL-2, the CTL derived from PBMNC stimulated by IL-2 (100 U/ml), the cytolytic activity of T-pC53-SN3 against Calu-6 cell line showed a significant increase, but cytolytic activity was 56.79 +/- 15.67 and 39.33 +/- 9.88, respectively, when effect cells: target cells was 10:1. The expression of the CD(8), CD(69), and CD(45)RO/CD(8) of T-pC53-SN3 cells increased significantly, but that of CD(3), CD(4), CD(86), ect, was not significantly different from those of T-pCMV-neo.

Conclusions: It showed that DC transfected by p53 gene could induce potent HLA-A(2) restrictive CTL to kill tumor cell efficiently.