Fishing therapeutic T-cell receptors in healthy donor blood, is safety predictable?

Adoptive transfer of genetically modified cells is close to becoming mainstream therapy for hematological malignancies (1). It entails the addition of targeting receptors in an effector cell (T cell or NK cell). To date, two main types of receptors have been exploited: a synthetic construct known as chimeric antigen receptor (CAR) which is comprised of the fusion of an antibody binding domain with a signaling transmembrane receptor or a T-cell receptor (TCR) which is the natural targeting protein of a T cell. Both receptors are expected to guide effector cells to recognize the tumour and to kill it. Astonishing clinical successes were reported using CAR targeting the B-cell lineage marker CD19, whereas TCRs have been harder to exploit (1). The main advantages of CARs over TCRs reside in their high affinity and MHC-independent binding, the latter rendering their use universal.