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Chimeric Antigen Receptor (CAR) T-cells hold promise as a future treatment option for Multiple Myeloma (MM). To read more about CAR T-cells see our MM Hub article: Original Review: Driving forward with CAR-T Therapy - what does this mean for MM? One of the biggest factors in the success of a given CAR T-cell is whether the target antigen is specific and has limited off-target effects. One of the targets under investigation is SLAMF7 (signaling lymphocytic activation molecule), also known as CD319, CS-1 and CRACC. SLAMF7 has a receptor tyrosine switch motif (ITSM), through which it modulates the function of immune cells. It is expressed on pro-B cells and plasma cells, and high expression is retained on malignant plasma cells, as well as the precursor states of monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma (SM). This expression is also retained following intensive therapy, and importantly expression appears to be limited to hematological cells only.
A SLAMF7-CAR construct has been developed by Tea Gogishvili and Sophia Danhof, led by Michael Hudecek, and in collaboration with Hermann Einsele, all from the University of Wurzburg, Germany, and the findings from their initial pre-clinical study to test the resulting CAR T-cells were published in Blood on 1st November 2017.
This well-designed pre-clinical study reveals highly promising data for the SLAMF7 CAR-T construct developed with the aim of targeting MM. The resultant SLAMF7 CAR T-cells were highly functional against cell lines, patient cells and in a xenograft model. In addition, whilst they led to some degree of depletion of the normal lymphocyte compartment, selective fratricide of only a fraction of normal cells was observed, leaving a functional immune compartment with efficient anti-viral capacity. We eagerly await this construct entering into early phase clinical trials.
ASH 2019 | Practice-changing abstracts in multiple myeloma
The Multiple Myeloma Hub has developed a downloadable resource, which provides an update on the practice-changing abstracts in multiple myeloma from ASH 2019 in preparation for ASH 2020.
Supportive care: managing infection in myeloma | An interview with Heinz Ludwig
Professor Heinz Ludwig spoke to Fiona Chaplin about the importance of supportive care in myeloma, focusing on the treatment and management of infection.
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