Anti-tumor Efficacy In Tumor Of CIK(Cytokine Induced Killer Cell) Combined With Gene Therapy Of Antibody

Cytokine induced killer (CIK) cells is a population of immune cells generated in vitro by the induction of several cytokines from peripheral blood monouclear cells (PBMCs). CIK cells are thought to be the preferential immune cell for next generation antitumor adoptive cellular immunotherapy. The important factors that influence the antitumor ability of CIK cells contain the quantity of their proliferation and activity in vitro. Therefore, sufficient cells and excellent survival status are the premises of CIK adoptive therapy.Antibodies can specifically inhibit the growth and metastasis of tumor cells by ADCC,CDC or phagorytosis. Antibodies have the characteristics of accurate targeting activity, low toxicity and high efficacy during tumor therapy, but still have some problems as follows: First of all, large quantity and high purity of antibodies are required for tumor therapy, the cost of antibody production is high, and the great majority of domestic patients can't afford the fancy medical expenses; Secondly, large-scale, high-density mammalian cell culture is a world-wide difficult problem, and the technology is shared only by a very few international companies, like Genentech Inc. in USA; Finally, the relative molecular mass of the antibody is bigger, the inner tissues in the solid tumor is compact, antibodies have a poor penetrability and also have a difficulty in entering tumors, and therefore their treatment efficacy against solid tumors in bulk mass is not unfavorable.The study optimized the isolation and culture protocol of CIK, improved the percent recovery of PBMCs from peripheral blood, and succeeded in extending CIK cells to 1011. The full-length gene of avastin was inserted into the expression cassette of Ad/AAV chimeric virus, and then the Ad/AAV chimeric virus expressing antibody avastin was constructed successfully. The chimeric virus combines the infection ability of Ad and the long lasting expression advantage of AAV, and therefore can efficiently infect CIK cells and express the antibody in CIK cells over a long period of time. In addition, the study combined the targeting safety of CIK immunotherapy and the validity of antibody gene therapy system, and CIK cells were used as the delivery vector of avastin gene therapy system and optimized the performance of the whole system.We have finished the foundation work of the plan and a lot of work still need to be done next。...