Therapeutic effect of autologous cytokine-induced killer cells on patients with liver cirrhosis caused by HBV infection / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To observe the therapeutic effect of autologous cytokine-induced killer cells (CIK) on HBV DNA positive patients with liver cirrhosis.</p><p><b>METHODS</b>HBV DNA positive 33 patients with cirrhosis were treated with CIK. Before and after cultured in vitro and post-treatment, CD3+, CD3+CD4+, CD3+CD8+, CD3+CD56+ cells, mDC and pDC were detected by flow cytometry. The indexes of virus and liver function were compared between pre- and post-treatment.</p><p><b>RESULTS</b>CD3+, CD3+CD8+ cells and CD3+CD56+ cells were higher after cultured in vitro and after transfused back than those before culture (91.5 +/- 10.3, 74.4 +/- 9.9 vs. 67.9 +/- 12.8; 60.9 +/- 15.5, 37.3 +/- 15.1 vs. 27.9 +/- 10.9; 18.4 +/- 11.7, 14.5 +/- 7.5 vs. 10.6 +/- 7.1). The percentages of mDC and pDC also increased after-treatment vs. pre-treatment (0.54 +/- 0.18 vs. 0.70 +/- 0.29; 0.26 +/- 0.13 vs. 0.41 +/- 0.25). HBV DNA became undetectable in 12 patients and decrease exceeded 100 times in 4 patients after treatment. HBeAg became undetectable in 10 of 14 patients who were HBeAg positive pretreatment patients, among them 2 patients had HBeAb sero conversion. The liver function was improved after treatment. All patients tolerated the treatment.</p><p><b>CONCLUSION</b>CIK treatment can increase immune effector cells and has some antiviral effect and is safe.</p>

Sequential analyses of circulating HBV specific T helper cell response in chronic hepatitis B patients receiving antiviral treatment / 中华实验和临床病毒学杂志

<p><b>BACKGROUND</b>To investigate the frequency of circulating HBV specific T helper cell and evaluate its association with serum levels of HBV DNA before and during lamivudine treatment in patients with chronic hepatitis B.</p><p><b>METHODS</b>The frequency of circulating HBV specific T helper cells in response to HBcAg in 25 chronic HBV-infected patients was determined by Elispot assay; serum HBV DNA was quantitated by real-time PCR.</p><p><b>RESULTS</b>The frequency of HBV specific T helper cell before antiviral treatment (47.30 +/- 25.50 SFCs /1 x 10(6) PBMC) was significantly higher than that at the third month of therapy (23.10 +/- 18.45 SFCs /1 x 10(6) PBMC, P < 0.05). All 8 patients observed dynamically had decreased frequency of HBV specific T helper cell at the third month of therapy; six patients with serum HBV DNA level reduced had higher frequency of HBV specific T helper cell before treatment than 2 patients without serum HBV DNA level decrease.</p><p><b>CONCLUSION</b>HBV specific T helper cell response at the time of hepatitis flare in chronic hepatitis B patients was significantly augmented compared to that at the time of catabasis.</p>

Growth inhibition of human hepatocellular carcinoma xenograft in nude mice by combined treatment with human cytokine-induced killer cells and chemotherapy / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To compare the inhibitory effects of cytokine-induced killer (CIK) cells alone, chemotherapeutic drug alone, and CIK cells combined with chemotherapeutic drug on the growth of hepatocellular carcinoma (HCC) cells transplanted in nude mice.</p><p><b>METHODS</b>Peripheral blood mononuclear cells (PBMC) collected from five healthy donors by blood cell separator were incubated in vitro to induce CIK cells in the presence of interferon-gamma (IFN-gamma), IL-2 and anti-CD3 monoclonal antibody (mAb). The phenotype of CIK cells was characterized by flow cytometric analysis. BEL-7402 HCC cells were inoculated subcutaneously to nude mice. On day 5, at the inoculation site were injected normal saline (group 1), CIK cells (3 x 10(7) and 6 x 10(7), group 2 and 3), mitomycin-C (MMC 80 microg in 0.2 ml, group 4), and CIK cells combined with MMC (group 5), respectively.</p><p><b>RESULTS</b>The percentage of CD3(+), CD3(+)CD8(+), CD3(+)CD56(+), CD25(+) cells increased from 64.0%, 28.0%, 7.8%, and 9.1% to 94.7%, 67.7%, 61.3%, and 84.0% respectively after cytokine induction. The percentage of CD3(+) and CD3(+)CD8(+) cells remained at high levels during incubation period, but that of CD25(+) and CD3(+)CD56(+) cells peaked respectively on day 7 and 13 and then declined. During the 90-day observation, the tumor formation rates were 100%, 70.0%, 80.0%, 70.0% and 66.7%; and the mouse survival rates were 10.0%, 60.0%, 40.0%, 50.0% and 75.0%, respectively from group 1 to group 5. Compared to the other groups, in the combined therapy group of mice, not only the tumor grew slowly and but also showed more marked tissue necrosis.</p><p><b>CONCLUSION</b>The growth inhibitory effect on human HCC transplanted in nude mice of combined CIK cells and MMC treatment is more potent than that of CIK cells or MMC alone.</p>