Effects of interleukin-2 transduction on the human hepatoma cell lines using retroviral vector

Gene therapy, using cytokine gene transduction, aims to increase the antige nicity of tumor cells, and to activate the immune effector cells, and there by inducing tumor regression. With regards to in vitro sensitivity to Perip heral blood monocytes and in vivo tumorigenic activity we compared the diff erences between parent hepatoma cell lines and interleukin-2 (IL-2) transdu ced hepatoma cell lines using N(2)A/IL-2 and LNC/IL-2 retrovirus. IL-2 secr etion was 186 pg/10(6) cells/24 h in SK-Hep1 cell line and 147 pg/10(6) cel ls/24 h in Hep-3B cell line with N(2)A/IL-2 retroviral vector and was 55,00 0 pg/10(6) cells/24 h in Hep-3B cell line with LNC/IL-2 retroviral vector. In vitro sensitivity to peripheral blood monocytes was increased by 163.8-2 54% in IL-2 transduced hepatoma cell lines (Hep-3B/LNC/IL-2, Hep-G2/LNC/IL- 2) compared to those of the parent cell lines. The turner was formed in 1 o f 3 BALB/c mice and all 3 nude mice with the injection of 1 x 10(7) cells. Simultaneous injection of 1 x 10(7) cells of the parent cell line (Hep-3B) into the right flank and IL-2 transduced cell line (Hep-3B/LNC/IL-2) into t he left flank of the three BALB/c mice and of 5 x 10(5) cells for the three nude mice resulted in a complete regression of the IL-2 modified tumor cel l line (Hep-3B/LNC/IL-2) in 3 weeks and the parent cell line (Hep-3B) in 5 weeks. After injection of 1 x 10(7) cells into five other nude mice, the tu mor of the IL-2 transduced hepatoma cells (Hep-3B/LNC/IL-2) gradually disap peared, however, the tumor of the parent hepatoma cell line initially decre ased and then gradually regrew 20 days later. In conclusion, IL-2 transduce d hepatoma cell lines secreting IL-2 became more sensitive to peripheral bl ood monocytes. IL-2 secretion by LNC/IL-2 retrovirus from the hepatoma cell lines was more prominent compared with that by N(2)A/IL-2 retrovirus. IL-2 transduction into the hepatoma cells resulted in increased antigenicity to the tumors formed by IL-2 transduced hepatoma cell line and parent cell li ne, which leads the regression of the tumors. However, the higher the tumor burden, the less efficient tumor regression by IL-2 transduction into the hepatoma cell line in nude mice was observed.