Chimeric antigen receptor modified T cells: Does receptor design and cell product composition matter?


Session type:

Stanley Riddell1,2
1Fred Hutchinson Cancer Research Center, 2University of Washington, Seattle, USA


The adoptive transfer of T cells modified with synthetic receptors that selectively target molecules expressed on tumour cells is emerging as a potentially disruptive therapy for human B cell malignancies, and is likely to have applications in solid tumours. The design of these chimeric antigen receptors (CARs) has largely been empiric and needs to be tailored for individual target molecules, and perhaps for different malignancies.Our lab has focused on discovering and validating novel targets for CAR T cell therapy on solid tumours that do not cause toxicity to normal tissues, and on optimising the design of CARs that recognise these molecules to promote effective T cell signalling. Studies directed towards validating ROR1 as a target for therapy of lung cancer and other solid tumours will be presented. A second focus of the lab is on defining optimal compositions of CAR modified T cell products for therapy of CD19+ hematologic malignancies that may provide for more reproducible in vivo efficacy. I will discuss the in vitro and animal model data that provide the rationale for deriving therapeutic T cells from defined subsets and present the results in the initial patients enrolled on the first clinical trial in which CD19 CAR T cells are manufactured from selected T cells and formulated in a defined product composition.