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Pre-clinical evaluation of NKT-cells in multiple myeloma (FWOKN235)

Multiple myeloma is still considered as the second most prevalent haematological malignancy and despite recent progresses in treatment options, MM still remains fatal for most patients. One of the new emerging strategies to target MM is using a patient's immune system to target the tumor. However, cancer cells can evade the immune system and tumor surveillance is often impaired. Therefore new drugs are being studied which can activate the immune system directly, thus overcoming this impairment.
The immune system can be divided in 2 groups, the innate system containing macrophages and NK cells and the adaptive system containing B and T cells. Within the T cells a relatively new member has been identified, the NKT cell which shows characteristics of both NK cells and T cells. Furthermore, NKT cells are CD1d restricted. A couple of studies on NKT cells in MM have been performed, showing that CD1d becomes downregulated in late stages of the disease and that NKT functionality has been impaired. However no preclinical data on activating these cells in MM is available yet.
In this project we will use the syngeneic immune competent 5T33MM mouse model to test a new activator of NKT cells preclinically. We will first characterize the NKT population in these mice and test their functionality against 5T33MMvv cells and a CD1d transduced 5T33MMvt cell line. We will then compare the efficiency of a new 6'-derivatised alpha-galactosylceramide analogue to regular alphaGalCer in its capacity to activate NKT cells and reduce tumor burden both in vitro and in vivo.
This study will provide new insights in the relatively young field of immunotherapy in MM. If proven useful, the ability to activate this mediator of immune surveillance could lead to new therapeutical targets.
Date:1 Jan 2011 →  31 Dec 2011
Keywords:Stem Cell, Blood, Coagulation, Myeloma, Immunology, Microbiology, HLA, Hematology, Lymphoma, cancer, Bone Marrow Transplantation
Disciplines:Basic sciences, Biological sciences