Multiple myeloma (MM) is a haematologic malignancy characterized by the expansion of monoclonal plasma cells in the bone marrow. It is associated with serum or urine monoclonal protein and organ damage including renal failure, anaemia, hypercalcaemia and bone lesions. Despite recent improvements MM still remains an incurable disease. Previous studies have shown that the adoptive transfer of autologous T-cells modified to express chimeric antigen receptors (CAR) is effective in cases of acute and chronic lymphoid leukaemia. However, the adjustment of CAR-T-cell therapy to MM is hindered by the scarcity of antigens specific to the tumour plasma cells. Most candidate targets are shared by healthy tissues, and entail high risks of toxicity. Therefore several strategies have been proposed to regulate CAR-T-cell function as well as to enhance CAR-T-cell specificity against tumour cells. In this article we summarize the surface markers that have been investigated as targets to eliminate MM plasma cells and the MM-specific CARs that have been developed to date. Then we describe the different CAR-T-cell designs that could be applied in the case of MM to circumvent current problems of toxicity.
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April 2016
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Cover Image
Endoplasmic reticulumendosome contact sites. This pseudo-colored electron microscopy image shows the formation of inter-organelle membrane contact sites between late endosomes (magenta) and the endoplasmic reticulum (ER; green). This tethering results from the interaction between two ER-anchored proteins (VAP-A and VAP-B) and the late endosomeanchored protein STARD3NL. Mitochondria: brown; nucleus: blue. For further details see pp. 493-498. Image kindly provided by Fabien Alpy. - PDF Icon PDF LinkTable of Contents
Review Article|
April 11 2016
Development of chimeric antigen receptors for multiple myeloma
Carolina Martínez-Cingolani;
Carolina Martínez-Cingolani
1
*INSERM 1126 Unit, Institut Universitaire d'hématologie, Hôpital Saint Louis, 75475 Paris, France
1To whom correspondence should be addressed (email carolina.martinez-cingolani@inserm.fr).
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Jean Christophe Bories
Jean Christophe Bories
*INSERM 1126 Unit, Institut Universitaire d'hématologie, Hôpital Saint Louis, 75475 Paris, France
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Publisher: Portland Press Ltd
Received:
February 04 2016
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2016 Authors; published by Portland Press Limited
2016
Biochem Soc Trans (2016) 44 (2): 397–405.
Article history
Received:
February 04 2016
Citation
Carolina Martínez-Cingolani, Jean Christophe Bories; Development of chimeric antigen receptors for multiple myeloma. Biochem Soc Trans 15 April 2016; 44 (2): 397–405. doi: https://doi.org/10.1042/BST20150280
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