Engineering CAR-T cells: Design concepts
Despite being empirically designed based on a simple understanding of TCR signaling, T cells engineered withchimeric antigen receptors (CARs) have been remarkablysuccessful in treating patients with advanced refractoryB cell malignancies. However, many challenges remainin improving the safety and efﬁcacy of this therapy andextending it toward the treatment of epithelial cancers.Other aspects of TCR signaling beyond those directlyprovided by CD3z and CD28 phosphorylation strongly. inﬂuence a T cell’s ability to differentiate and acquire fulleffector functions. Here, we discuss how the principles ofTCR recognition, including spatial constraints, Kon/Koffrates, and synapse formation, along with in-depth analysis of CAR signaling might be applied to develop saferand more effective synthetic tumortargeting receptors.