Towards safe and effective CD38-CAR T cell therapy for myeloma

Abstract

Immunotherapy is a promising field within cancer therapy. The recent progresses resulted in 'Immunotherapy for the treatment of cancer' as break-through of the year in 2013. This was partly due to the great successes with Chimeric Antigen Receptor (CAR) T cell therapy. With CAR T cells, recognition takes place via a cleverly synthesized receptor made in the laboratory on the basis of an antibody, which has been made part of the T cell receptor via genetic manipulation. Clinical studies with CAR T cells have shown how strong this anti-tumor weapon is. In order to make CAR T cell therapy accessible to more patients, we focus on different targets, such as CD38 for multiple myeloma. In the past 30 years, the treatment of multiple myeloma has greatly improved, with improved survival rates. Very recent research has shown that antibodies against CD38 have proven clinical benefit. CD38 is a molecule that is present in large numbers (high expression) on multiple myeloma cells. In this thesis we study the possibility to target CARs against CD38 and we studied ways to improve the therapy and reduce toxicity. These important aspects of the development of CAR T cells have been studied and presented in this thesis: towards a safe and applicable CAR T cell treatment for multiple myeloma.