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Cell Transfer Therapy for Cancer: Past, Present, and Future

DOI: 10.1155/2014/525913

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Abstract:

Cell transfer therapy for cancer has made a rapid progress recently and the immunotherapy has been recognized as the fourth anticancer modality after operation, chemotherapy, and radiotherapy. Lymphocytes used for cell transfer therapy include dendritic cells, natural killer (NK) cells, and T lymphocytes such as tumor-infiltrating lymphocytes (TILs) and cytotoxic T lymphocytes (CTLs). In vitro activated or engineered immune cells can traffic to cancer tissues to elicit persistent antitumor immune response which is very important especially after immunosuppressive treatments such as chemotherapy. In this review, we overviewed recent advances in the exploration of dendritic cells, NK cells, and T cells for the treatment of human cancer cells. 1. Introduction Inspired by the observation of complete tumor regression in a male patient with recurrent sarcoma after a postoperative infection of erysipelas, Coley treated advanced sarcoma patients with mixed toxins of streptococcus erysipelas and bacillus prodigiosus in 1891 [1, 2], thus starting the history of the immunotherapy for human cancers. Unfortunately, limited progress has been achieved since then. Recently, the great successes in adoptive cell transfer therapy (ACT) and the development of anti-cancer antibodies such as Ipilimumab rekindled the interest of the scientific community in the anticancer immunotherapy and cytokine treatments. Now, the immunotherapy has been recognized as the fourth anticancer modality after operation, chemotherapy, and radiotherapy. There are two types of immunotherapy for cancer, active immunotherapy and passive immunotherapy. The active immunotherapy mainly refers to vaccines, immune adjuvants, and cytokines, while the passive therapy consists of immune modulating antibody-based therapy and adoptive immunotherapy. Active immunotherapies can activate endogenous immune system and passive immunotherapies provide or strengthen immune reaction in cancer patients by infusing antibodies or effector cells produced in vitro. Among the active immunotherapy, cytokines including interleukin-2 (IL-2), interleukin-12 (IL-12), granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor (TNF)-α, and interferons (IFNs) are secreted by immune cells and play pivotal roles in the active immunotherapy. IL-2 is an important growth factor for lymphocytes. It has been proved by FDA to treat advanced melanoma and renal carcinoma. However, the serious systemic toxicities of high-dose IL-2 restrict its wide application [3]. Depending on the different immunocytes transferred, cell

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