Elvira D’Ippolito

Abstract Recent studies suggest that Chimeric Antigen Receptor (CAR) binding affinity to its ligand affects CAR-T-cell functionality. Affinity engineering towards lower binding strengths might mitigate therapeutic side effects arising from intense CAR-T-cell activation as well as tumor relapse due to antigen-escape or limited persistence of CAR-T cells during sustained activation via high-affinity receptors.

Editor’s summary CD8 T cell responses are detected after SARS-CoV-2 mRNA vaccination, but how these vaccines shape the expansion of T cell clones is unclear. Kocher et al. characterized CD8 T cell responses in 29 individuals receiving three mRNA vaccinations before breakthrough infection. Using flow cytometry, ELISpot, single-cell RNA and T cell receptor (TCR) sequencing analyses, and transgenic TCR reexpression, they examined the effects of TCR avidity on the expansion of T cell clones.

Abstract T cells can be reprogrammed with transgenic antigen recognition receptors, including chimeric antigen receptors and T cell receptors, to selectively recognize and kill cancer cells. Such adoptive T cell therapies are effective in patients with certain haematological cancers but challenges persist, including primary and secondary resistance, a lack of efficacy in patients with solid tumours, a narrow range of targetable antigens, and time-consuming and complex manufacturing processes.