Tumor-targeting expression of a new tumor suppressor gene HCCS1 and its tumor-selective inhibitory effects on hepatocellular carcinoma / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To construct a tumor-targeting recombinant adenovirus vector containing hepatocellular carcinoma suppressor gene HCCS1 to enhance the safety of tumor treatment.</p><p><b>METHODS</b>CCK-8 assay was used to observe different inhibitory effects on normal and malignant liver cells with high expressions of HCCS1 protein. The relative transcriptional activity of PEG-3p was quantified by luciferase assay. Recombinant adenovirus Ad-PEG-3p-HCCS1 was packaged with AdEasy system and confirmed by PCR. The tumor-targeted expression of HCCS1 protein in cells infected with Ad-PEG-3p-HCCS1 was determined by Western blot. Crystal violet assay and MTT assay were applied to observe the selective anti-tumor effects of the newly constructed virus in vitro.</p><p><b>RESULTS</b>A higher inhibitory rate of about 60% was found in BEL-7404 and SW-620 than that in L02 and NHLF 96 h after the high expression of HCCS1. Luciferase assay showed 3.9-, 4.7-, and 1.5-fold transcriptional activity in BEL-7404, BEL-7405 and QGY-7703 respectively, in comparison with that in L02. Ad-PEG-3p-HCCS1 was constructed successfully and was verified by PCR. Western blot indicated that high expression of HCCS1 could be induced in BEL-7404 and QGY-7703 but not in L02. Crystal violet assay and MTT assay showed that it remarkably reduced the toxicity to L02 but still had enough antitumoral effect on Ad-CMV-HCCS1.</p><p><b>CONCLUSIONS</b>With high expression of HCCS1 the tumor cells we used are being inhibited more. PEG-3p has the tumor-selective driving function in malignant liver cells. Our recombinant adenovirus Ad-PEG-3p-HCCS1 can tumor-targeting induce HCCS1 expression in tumor cells, which can improve the safety of gene therapy with HCCS1.</p>

Experimental induction of immunity by anti-idiotypic vaccines against small-cell-lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the efficacy of anti-idiotype antibody 3F6 and its single-chain variable fragment (3F6 ScFv) to induce humoral and cellular immune responses against small-cell-lung cancer (SCLC).</p><p><b>METHODS</b>3F6 and 3F6 ScFv (Ab2) were used to immunize BALB/c mice. The reaction of antibodies (Ab3) with specific antigen on NCI-H128 cells was tested by ELISA and Western blot, and the antibody binding inhibition assays were performed by competitive Western blot. Cellular immunity against SCLC induced by Ab2 was detected by a delayed-type hypersensitivity response and mouse lymphocyte proliferation assay.</p><p><b>RESULTS</b>The sera immunized with Ab2 showed significant reaction (P < 0.001, as compared to control sera) with SCLC-specific antigen on NCI-H128 cells and specifically competed the binding of 2F7 (Ab1) to the specific antigen. DTH responses challenged with NCI-H128 cells were significantly (P < 0.001) stronger in mice immunized with Ab2 as compared to mice immunized with normal mouse IgG. T cell proliferation was significantly higher in Ab2-immunized mice (P < 0.05) than in control mice.</p><p><b>CONCLUSION</b>The two kinds of anti-idiotypic antibodies successfully mimic the SCLC-specific antigen on NCI-H128 cell and induce strong humoral and cellular immune responses to SCLC-specific antigen in syngeneic mice. They may become novel vaccines against human small-cell-lung cancer and worthy of further investigation.</p>