| Lymphotactin enhances the antitumor efficacy of dendritoma formed bydendritic cells and mouse hepatocellular carcinoma cellsDepartment of Hepatobiliary Pancreatic Surgery. Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, College of Medicine,Zhejiang University, ChinaM.D Student: Zhang HaoSupervisor: Pro. Zheng Shu-senHepatocellular carcinoma (HCC) is one of the most common malignances in our country. The incidence and mortality rates are high, the treatment is challenging, and the prognosis is still poor. Now the treatment option is multimodality therapy in which surgical resection plays the most important role. But the high incidence of recurrence and metastases remains a critical issue other than the improvements in radiological diagnosis, surgical techniques, perioperative management and the availability of downstaging resection and liver transplantation which all have contributed to increase the resectability rates, we still lack of definitive method to prevent and treat recurrences and metastases of HCC. So it is the key role to find a novel method to overcome this obstacle. Following the quick development of modern molecular biology and gene engineering. Biotherapies based on the development of immunology showed promising results, and gained popular recognition. As we attain a deeper understanding of the characteristics of HCC, we may be more powerful to exploit the biofeature and immune response of HCC and use it as a platform on which to build a successful therapeutic strategy to fight cancer. The increasing knowledge of the mechanisms involved in immune reactions against cancer cells has lead to the development of experimental and clinical immunotherapeutic approaches for the treatment of cancer patients and the prevention of cancer recurrence. Biotherapies recently attracting much more attention and would probably be the forth therapy model except operation, radiation and chemotherapy.Dendritic cell (DC) is the most potent antigen-presenting cell at present, which play a key role in the initiation of immune response. These cells are considered promising tools and targets for immunotherapy. They possess an extraordinary capacity to capture and processantigen and contain all that is needed to stimulate T cell immunity, including high level of major histocompatibility complex, costimulatory molecules, and adhesion molecules as well as a variety of immunologically important cytokines such as IL-1. TNF-a, and IL-12. These properties, coupled with the fact that it is now possible to generate, ex vivo, large numbers of functional DCs from a patient's peripheral blood monocytes or CD34 haemopoietic stem cells, have led to considerable interest in the use of dendritic cell vaccines as a means to induce antitumour immunity. There were different strategies that had been applied in animal experiments or clinical trials to deliver antigen to DC. such as pulsing synthetic or eluted peptides, transfection with cDNA or RNA encoding known TAA, loading tumor lysate or tumor RNA. However, these approaches are currently limited for clinical application, as few human tumor rejection antigens have been identified. The high polymorphism of the human HLA system has also made it difficult to identify tumor-associated peptides as a vaccine for cancer therapy. In addition, using tumor lysate or DNA/RNA loading method creates the risk of inducing immune responses against numerous self-antigens shared with normal cells.Gong et al first used bone marrow derived DCs as fusion partners for tumor cells in 1997, which broadened the vision of the vaccine research. Kugler et al generated hybrids of autologous tumor cells and allogeneic DCs using electrofusion techniques in 2000, which showed that the hybrid cell vaccination was a safe and effective immune therapy for human metastatic renal cell carcinoma. These promoted the possibility of treatment common human tumours with dendritoma. To date there has seldom reported research on DC fusion immunotherapy for HCC, and has no related resea...
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