Continuous Release Of Endostatin And Interferon-γ From Microencapsulated Engineered Cells For Tumor Therapy

Malignant tumor is one of the mainly hazard for human health. The therapy for cancer is a comprehensive method mainly including surgery, chemotherapy and radiotherapy. Cancer is a systemic disease, so the surgery and radiotherapy are not sufficient to extirpate or eliminate the cancer cells completely from the patients, and the disease would be in relapse or metastasis even with effective treatment. On the other hands, although the chemotherapy really can get some remission rates, patients always can not tolerate it due to the severe toxic and side effects. And in the long-period treatment procedure, patients could get resistance to some chemotherapy drugs and lead to the failure of chemotherapy or relapse of tumor. Recent years, the tremendous progress has been developed in the biologic therapy which has been called the forth pattern for cancer treatment, and it has been becoming more and more important in the treatment of cancer.The application research of biological therapy for cancer mainly included: ①Cytokine gene-engineered therapy of cancer; ② Adoptive cellular immunotherapy of cancer; ③ Monoclonal antibody-directed therapy for cancer; ④Tumor vaccine and ⑤Cancer gene therapy. Among all of them, the cytokine gene-engineered therapy has been comprehensive used in the treatment of cancer, and the further study of the cytokine such as the interferon (INF), interleukin-12 (IL-12), and cloning stimulating factor (CSF) has got a lot of progress. Although recombinant cytokine proteins have demonstrated potent antitumor effects when injected systemically, a lot of problems had not been overcome properly. ①Because of the shorter half life, the cytokines were rapidly eliminated and biodegraded from the blood. To maintain the therapeutic concentration of serum, the recombinant cytokine proteins were administered by continuous injected intravenously or discontinuous injection subcutaneously in a large dosage. The too large amount of the drugs could cause the severe toxic and side effect. On the other hands,the purity and activity of the recombinant cytokine proteins were not sufficient thoroughly, which cause the patients the Influenza-like symptom (for example fever) easily. Recent years, cytokine gene therapy has received considerable interest in cancer biologic therapy. The local transfer of cytokine genes as a means for gene therapy can circumvent the systemic toxicity and provide effective, persistent local cytokine levels for immune cells activation. Several studies using an ex vivo cytokine gene therapy approaches have produced encouraging results, showing that murine fibroblasts or tumor cells transduced in vitro with cytokine cDNA, using a retroviral vector or non-viral vector, were able to induce antitumor immune responses in the absence of apparent toxicities. This strategy, however, has many obstacles precluding successful clinical application: autologous somatic cells or tumor cells may be difficult to be cultured and transfected, and selection for transfected cells may require prolonged culture and the attendant costs of these process may be expensive. Moreover, another progress need to be developed in the future including the gene transfection efficacy, the gene expression control and the vector. To avoid these potential disadvantages, an alternative approach to obtain prolonged local cytokine secretion is to use the microencapsulated engineered cells.Microencapsulated cell is the microcapsule entrapping viable cells within the confines of semi-permeable membranes. Microcapsules are almost exclusively produced from hydrogels since they hold a number of appealing features. ① Semi-permeability, which provide a high degree of permeability for low-molecular-mass(Mr) nutrients, water, oxygen and metabolites including the low-molecular-mass(Mr) biological activated factors. ②Immunoisolation: A further advantage of microcapsules is that the capsule contents are protected from immune rejection because leucocytes and antibodies cannot penetrate the capsule. This allows allogeneic or xenoge...