title: Development of chimeric antigen receptors for multiple myeloma.
abstract: 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.
authors.affiliation: INSERM 1126 Unit, Institut Universitaire d'hématologie, Hôpital Saint Louis, 75475 Paris, France carolina.martinez-cingolani@inserm.fr.
authors.forename: Carolina
authors.initials: C
authors.lastname: Martínez-Cingolani
authors.affiliation: INSERM 1126 Unit, Institut Universitaire d'hématologie, Hôpital Saint Louis, 75475 Paris, France.
authors.forename: Jean Christophe
authors.initials: JC
authors.lastname: Bories
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D064593:Heterografts; D006801:Humans; D009101:Multiple Myeloma / Q000276:immunology / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D011948:Receptors, Antigen, T-Cell
keywords: antibody; chimeric antigen receptor; multiple myeloma; plasma cells