Effects Of Systemic Immunity In Mice Implanted With Tumor Necrosis Factor-alpha Gene-transduced

Effect of systcmic immunity in mice implanted withtUmor necrosis factor-alpha gene-transducedBEL-7404 cellsPostgratuatc: Qin Xin-GanTutors: Lu Yun-Fei, Lin Jin-Lihg, Li Shao-Sen, et aIANSmCTObjective: To investigate the feasibility of a human tumornecrosis factor-alpha (TNF- Q ) gene-transduced human hepaticcarcinoma cell lines BEL-7404 used as tumor vaccine, and study theeffect of systemic immunity and proplylaxes in mice, inoculated withthe tumor vaccine.Mcthods: To evaluate the tUmor vaccine efficacy of mF- Qgene-transduced BEL-7404, mice were divided into five groups, andwere inoculated with TNF- Q gene-transduced BEL-7404 (BEL-7404- TNF), TNF-- Q gene-transduced BEL-7404 which irradiatedwith ooCo (BEL-7404-M-Co), BEL-7404, BEL-7404 irradiatedwith "Co(BEL- 7404-Co), respectiveIy. NormaI Saline was injected incontrol group. The natural ldller celI activity and the lymphocytetransformation rate of the mice splenocytes were assayed by Mrimethod, the contents of CD,+ CD.+ CD8+of T lymphocytesubpopuIation of the mice splenocytes was detected by SABCimmunohistochemical method. Observed the growth of hepaticcarcinOma H22, which implant in mice after being inoculated by thetumor vaccine. The apoptosis index of H22 was detected by TUNELmethod.2ResultS: The gene-transduced tumor cells, shll preserve theability to produce TNF- Q over 2 weeks, after irradiated with 80gydose of "Co, but their growth ability was lost completely. There arenot side effectS in the mice after inoculated with the gene-transducedtUmor vaccine. The natural ldller cell achvity of the BEL-7404-TNFgroup, the BEL-7404-wr-Co group, the BEL-7404 grouP, theBEL-7404-Co grouP and the control group is 66.26t6.77%,64.58t7.82%, 53.20t7.02%, 5l.44t7.83%, 27.06t5.25%, resPectiveIy.The CD.+ of the miCe sPlenocytes of the BEL-7404-TNF grOup, theBEL7404-W-Co group, the BEL-7404 grouP, the BEL-7404-Cogroup and the control group is 45.46tl.46%, 43.00tl.39%,38.66t1.80%, 33.90t4.81%, 34.12t3.56%, resPechvely. The CD8+ ofthe mice sPlenocytes of the BEL-7404-ThF group, the BEL-7404-M-Co group, the BEL-7404 group, the BEL-7404-Co group and thecontrol group is 31.68t1.53%, 29.52t2.17%, 25.66t2.75%,23.88t1.44%, 24.30t4.08%, resPechvely. The gene-transduced tumorvaccine group compared to the tUmor vaccine which did not transducewith TNF- Q gene and the controI group, the natural killer cellactivity and the population of CD.+, CD,+of the mice splenocytesincreased significantly(P<0.05 or P<0.0l). The tumorigenesis rate ofH22 in the mice of the BEL-7404-TNF group, the BEL-7404-TNF-Cogroup, the BEL-7404 group, the BEL-7404-Co group and the controlgroup is 50%, 50%,62.5%,75%,100%,respectively The sizeof H22 in the mice of the BEL-7404-TNF group, theBEL-7404-TNF-Co grOup, the BEL-7404 group, the BEL-7404-Cogroup and the control group is 1210.8t126.5mm', 1133-0t136.4mm',1424.4tl64.4mm', 1472.7t l86.0mm', l569.9t127.l mm',respectively (P<0.01or P<0.05). The weight of H22 in the mice of theBEL-7404-W grouP, the BEL-7404-wr-Co group, the BEL-7404group, the BEL-7404-Co group and the control group is32070.9?77.5mg,2191.7?26.2mg,3685.4?98.8mg,3804.5?51.9mg, 4154.1?19.4mg, respectively (P<0.01). The apoptosis index of H22 in the mice of the BEL-7404-TNF group, the BEL-7404-TNF-Co group, the BEL-7404 group, the BEL-7404-Co group and the control group is 3.73?.61%, 3.90?.71% 202+1.39%, 1.72?.89%, 0.65?.24%, respectively (P<0.01). The gene-transduced tumor vaccine group compared to the control group, the tumorigenesis rate of H22 was reduced, the growth of H22 was inhibited and the apoptosis of H22 was increased.Conclusions:Humantumornecrosisfactor-alphagene-transduced human hepatic carcinoma cell lines BEL-7404 can be used as tumor vaccine that can augment systemic immunity and be applied as tumor prophylaxis.