Cloning, Expression Of Interleukin-15 CDNA And Antitumor Effect Induced By Interleukin-15 CDNA-Transfected Lung Cancer Cells

Interleukin-15(IL-15) is a newly discovered cytokine that shares biological activities with IL-2. IL-15 not only promotes the proliferation and differentiation of T cell,NK cell and B cell, but also induces them to produce IFN-γ or TNF- α. Both in the thymic microenviroment and in the bone marrow microenviroment, IL-15 plays important roles on development, differentiation, proliferation and maturation of NK progenitors. IL-15 could induce stronger NK/LAK/CTL activity through increase of CD 18 and perform expression. IL-15 induces cytotoxicity two to three times higher than IL-2 in vitro. By using murine models, it has been shown that IL-15 is three to four times more potent than IL-2 in generating NK activity, but it is approximately one-third as potent as IL-2 in inducing LAK activity. The dose of IL-15 required to induce pulmonary vascular leak in mouse is six times higher than that of IL-2 required .The therapeutic index of IL-15 is superior to that of IL-2. These evidences suggested that IL-15 can produce significant anti- tumor roles. Therefore, IL-15-gene transfected tumor cells may be a hopeful cancer vaccine to generate specific antitumor activity.Recently, great progress has been made in the studies of cytokine gene therapy for cancer. The results in animal experiment demonstrated tumor cells that were transfected with cytokine gene may greatly improve the immunogenicity of the tumor cells, and induce local or systemic immune response of antitumor in vivo. Many cytokine gene, including IL-2,IL-4,IL-6,IL-7,IL-12,GM-CSF,TNF α,IFNγ, has been approved to apply in the pre-clinic investigation by RAC/FDA. Up to date, There is no report that IL-15-gene-transfected tumor cells may induce antitumor or anti- tumor metastasis .In this paper, IL-15 cDNA was amplified by RT-PCR from mRNA tthat were extracted from human adherent peripheral blood monocytes(PBMCs). These PBMCs were activated with 5 ug/ml of LPS of RPMI-1640 mediumfor four hours. The amplified cDNA sequence determined contains the open reading frame of human IL-15 and partial sequence of 5', 3' nontranslation termini. This...