|
Adoptive cell transfer (ACT) is the transfer of cells into a patient; as a form of cancer immunotherapy. The cells may have originated from the patient him- or herself and then been altered before being transferred back, or, they may have come from another individual. The cells are most commonly derived from the immune system, with the goal of transferring improved immune functionality and characteristics along with the cells back to the patient. Transferring autologous cells, or cells from the patient, minimizes graft-versus-host disease (GVHD) or what is more casually described as tissue or organ rejection. == History == In the 1960s, lymphocytes were discovered to be the mediators of allograft rejection in animals. Attempts to use T cells to treat transplanted murine tumors required cultivating and manipulating T cells in culture. Syngeneic lymphocytes were transferred from rodents heavily immunized against the tumor to inhibit growth of small established tumors, the first example of ACT.〔 Description of T cell growth factor interleukin-2 (IL-2) in 1976 allowed T lymphocytes to be grown ''in vitro'', often without loss of effector functions. High doses of IL-2 could inhibit tumor growth in mice. 1982 studies demonstrated that intravenous immune lymphocytes could treat bulky subcutaneous FBL3 lymphomas. Administration of IL-2 after cell transfer enhanced therapeutic potential.〔 In 1985 IL-2 administration produced durable tumor regressions in some patients with metastatic melanoma. Lymphocytes infiltrating into the stroma of growing, transplantable tumors provided a concentrated source of tumor-infiltrating lymphocytes (TIL) and could stimulate regression of established lung and liver tumors. In 1986 human TILs from resected melanomas were found to contain cells the could recognize autologous tumors. In 1988 autologous TILs were shown to reduce metastatic melanoma tumors.〔 Tumor-derived TILs are generally mixtures of CD8+ and CD4+ T cells with few major contaminating cells.〔 Israeli scientist Zelig Eshhar published a study in 1989 in which he replaced the T cell’s natural receptor. Responses were often of short duration and faded days after administration. In 2002, lymphodepletion using a nonmyeloablative chemotherapy regimen administered immediately before TIL transfer increased cancer regression, as well as the persistent oligoclonal repopulation of the host with the transferred lymphocytes. In some patients, the administered antitumor cells represented up to 80% of the CD8+ T cells months after the infusion.〔 Initially, melanoma was the only cancer that reproducibly yielded useful TIL cultures. In 2006 administration of normal circulating lymphocytes transduced with a retrovirus encoding a T-cell receptor (TCR) that recognized the MART-1 melanoma-melanocyte antigen, mediated tumor regression. In 2010 administration of lymphocytes genetically engineered to express a chimeric antibody receptor (CAR) against B cell antigen CD19 was shown to mediate regression of an advanced B cell lymphoma.〔 In 2009, a woman given T cells engineered to recognize colon cancer suddenly went into respiratory distress and soon died. By 2010, doctors had begun treating leukemia patients with CD19-targeting T cells with added DNA to stimulate cell division. As of 2015 trials had treated about 350 leukemia and lymphoma patients. Antigen CD19 appears nowhere in the body except on B cells, which go awry in lymphoma and leukemia. Loss of B cells can be countered with immunoglobulin.〔 In August 2012, Novartis donated $20 million to the University of Pennsylvania to build a cell-therapy center, based on data from three patients. Startups including Juno exploit the combination of aggressive tumors and FDA willingness to approve potential therapies for such ailments to accelerate approvals for new therapies.〔 To date, engineered T cells seem to quickly disappear from many patients. However, genetic engineering has allowed T cells to disable molecules called PD-L1 that turn T cells off, called checkpoint therapy.〔 Ten minute, single dose treatments costing $500,000 would be far less expensive than 2015 US hospital costs, which can exceed $2 million for a single leukemia patient.〔 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「adoptive cell transfer」の詳細全文を読む スポンサード リンク
|