Ross M. Kedl

Jan 2, 2025 | nature.com | Kole DeGolier |Michael C. Yarnell |Ross M. Kedl |M. Kohler |James P. Scott-Browne |Marc D’Antonio | +3 more

Although chimeric antigen receptor (CAR) T cells are effective against B-lineage malignancies, post-CAR relapse is common, and efficacy in other tumors is limited. These challenges may be addressed through rational manipulations to control CAR T cell function. Here we examine the impact of cognate T cell antigen experience on subsequent CD8+ CAR T cell activity. Prior antigen encounter resulted in superior effector function against leukemia expressing low target antigen density at the expense of reduced proliferative capacity and susceptibility to dysfunction at limiting CAR doses. Distinctive temporal transcriptomic and epigenetic profiles in naive-derived and memory-derived CAR T cells identified RUNX family transcription factors as potential targets to augment the function of naive-derived CD8+ CAR T cells. RUNX2 overexpression enhanced antitumor efficacy of mouse CAR T cells, dependent on prior cell state, and heightened human CAR T cell functions. Our data demonstrate that prior antigen experience of CAR T cells determines functional attributes and amenability to transcription factor-mediated functional enhancement. Here, Fry and colleagues examine the impact of antigen experience on subsequent CD8+ CAR T cell activity during the antileukemia response and show that RUNX2 overexpression enhances antitumor activity of these cells.

Aug 1, 2024 | biorxiv.org | Ross M. Kedl |Scott Thompson |Michael Harbell |John Manalastas

AbstractProtection from pathogens relies on both humoral (antibody-mediated) and cellular (T cell-mediated) responses. While infections robustly elicit both types of immunity, currently approved vaccine adjuvants largely fail to induce T cell responses on par with that instigated by infections. Our goal was to investigate the transcriptional programming that supports the formation of CD8+ T cells elicited by subunit vaccines compared to those elicited by infections.

Jul 10, 2023 | nature.com | Ross M. Kedl |Stephen C Jameson

CD8+ virtual memory T cells have been studied mainly for their antimicrobial functions but it seems that their descendants can contribute to inflammation and hair loss in the context of alopecia areata. The traditional conception of memory T cells is as the product of a response to foreign antigens. However, cells with memory-like properties also arise during normal T cell homeostasis.