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Chronic Myelogenous Leukemia (pp. 1-26) $25.00
Authors:  Müller, Ludmila and Pawelec, Graham (University of Tübingen Medical School, Germany)
Abstract:
The world-wide incidence of Chronic Myelogenous Leukemia (CML) is 1-2 cases per 100,000 people per year making it one of the four most common leukemias. Despite recent advances in the treatment of CML it is still commonly fatal within 5-7 years of diagnosis. Much circumstantial evidence points to the immunogenicity of CML, most impressively the well-established T cell-dependent GvL effect seen in bone marrow transplantation. However, only a small number of shared antigens expressed by CML cells have been identified as potential targets for T cell-mediated immune responses which might be exploited for immunotherapy. It may be that unique antigens expressed by individual tumors are more potent rejection antigens if the patient´s own T cells could be encouraged to react against them. In this review we will first detail the physiological and molecular characteristics of CML, briefly describe the treatment options that are currently available including the mechanism(s) of action and resistance to Imatinib,- a rationally designed, new and successful treatment for CML. We will then explain the tumor escape mechanisms in CML and new strategies in immunotherapy that strive to manipulate the immune system to recognise CML. With these insights we will go on to detail whether CML patient-derived PBMC and PBMC from healthy donors contain T cells specific for a range of peptides derived from BCR/ABL mHA, PR3, WT1, HAGE and other novel CML-associated antigens. We will review here our work which documents that mixed cultures of autologous T cells and dendritic cells of chronic-phase CML patients can give rise in vitro to sensitised T cells capable of recognising the patient´s tumor cells. Additionally, mixed autologous tumor cell / lymphocyte cultures, modified by the addition of cytokine cocktails, may also result in the generation of similarly sensitised T cells. These results could be exploited for adoptive immunotherapy, and possibly, after identification of the antigens recognised, also for active immunotherapy, ie. therapeutic vaccination. 


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Chronic Myelogenous Leukemia (pp. 1-26)