CARAT Objectives

Chimeric antigen receptors (CARs) are artificial surface receptors that can be introduced into somatic cells by genetic engineering and that act as recognition molecules like antibodies or T-cell receptors. In this respect, CARs are increasingly used for cellular therapy to redirect T-cells specifically towards killing of cancer cells (e.g. reviewed in: Brenner, 2012; Anurathapan et al., 2014).

Recent success stories of cancer therapy with CAR-modified T-cells have raised enormous scientific and public expectations to cure severely ill patients. For example, in a clinical trial on a highly aggressive form of acute lymphoblastic leukaemia (ALL) 89% of children and adults showed no evidence of cancer after receiving a CAR T-cell therapy. Although 6 patients subsequently relapsed from complete response, 64% of patients remained in complete response demonstrating the potential clinical benefit of this class of therapies (Grupp et al., 2013).

However, there are still many obstacles to overcome for translation into clinics and broad application. Most importantly, clinical manufacture of gene-modified T-cells is currently an enormously complex procedure that is handled in specialized GMP laboratories comprising many (open) handling steps like cell isolation, gene-modification, washing, feeding etc. As a result, failure rates and costs remain high, and the procedure is very difficult to spread to less specialized, local clinical centres. Hence, the number of patients that can be treated is restricted, and there is an urgent need for a simplified, safe and effective solution.