Adenovirus-mediated lymphotactin gene transfer improves therapeutic efficacy of cytosine deaminase suicide gene therapy in established murine colon carcinoma
| Autor: | Xuetao Cao, Dianwen Ju, D S Cheng, Q Tao, M Zhang, Hirofumi Hamada, W Zhang |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Male
Sialoglycoproteins Genetic enhancement Apoptosis Nucleoside Deaminases Biology Transfection medicine.disease_cause Adenoviridae Cytosine Deaminase Mice Interleukin 21 Tumor Cells Cultured Genetics Carcinoma medicine Animals RNA Messenger Molecular Biology Gene Lymphokines Mice Inbred BALB C Genetic transfer Cytosine deaminase Gene Transfer Techniques Genetic Therapy Suicide gene Flow Cytometry medicine.disease Chemokines C Immunity Active Colonic Neoplasms Cancer research Molecular Medicine Female |
| Zdroj: | Gene Therapy. 7:329-338 |
| ISSN: | 1476-5462 0969-7128 |
| DOI: | 10.1038/sj.gt.3301082 |
| Popis: | Lymphotactin (Ltn) is the sole member of C chemokines which attracts T cells and NK cells specially. Ltn gene was transferred in vivo to improve the antitumor efficacy of cytosine deaminase (CD) gene therapy. Upregulation of CD80 and CD54 on murine CT26 colon carcinoma cells was observed after combined transfection with adenovirus encoding CD (AdCD) and adenovirus encoding murine Ltn (AdLtn) followed by administration of 5-fluorocytosine (5FC) in vitro. AdCD/5FC treatment also increased the expression of CD95 and induced obvious apoptosis of CT26 cells. After combined treatment with AdLtn and AdCD/5FC, the pre-established murine model with subcutaneous CT26 colon carcinoma exhibited most significant tumor growth inhibition, and four of eight tumor-bearing mice were tumor free, while tumors in other mice grew more progressively. Examination of lymphocyte infiltration and cytokine gene expression in tumor tissue revealed that tumors from AdLtn/AdCD/5FC-or AdLtn-treated mice were heavily infiltrated with CD4+, CD8+ T cells and NK cells, and IL-2 and IFN-gamma mRNA expression were present in parallel with T cell and NK cell infiltration. Splenic NK and CTL activities increased significantly after the combination therapy. In vivo depletion analysis showed that NK cells, CD4+ T cells and CD8+T cells participated in the antitumor effect of the host with CD8+T cells being the main T cell subset responsible for the enhanced antitumor immune response. These findings suggested that increased immunogenicity and induction of apoptosis of the tumor cells, and efficient induction of local and systemic antitumor immunity of the host might contribute to the enhanced antitumor effects of the combined Ltn and CD suicide therapy. Gene Therapy (2000) 7, 329-338. |
| Databáze: | OpenAIRE |
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