Kole DeGolier

No functional NIH…no US scientists that spend their days making discoveries that save lives and drive US innovation and economic growth. This will negatively impact all Americans.

Yes. Exactly. One of (if not THE) best ROI for any govt spending.

Couldn't have done it without the help of many other people, including co-authors: Etienne Danis, Marc D'Antonio, Jen Cimons, Michael Yarnell, Eric Kohler, Ross Kedl, James Scott-Browne and my PhD advisor, Terry Fry! Also big thanks to @cuanschutz.bsky.social.

We expect our findings to provide useful insights toward understanding and modulating cellular states for more effective cell therapies in cancer and other diseases.

Finally, transcriptomic and epigenetic analyses reveal that the RUNX2 transcription factor is more active in memory-derived CAR T cells. Overexpressing RUNX2 in naive-derived CAR T cells enhances cytotoxicity without impairing proliferation, improving overall anti-tumor function.

We show that despite this stimulation, many functional traits characteristic of the ancestral T cell state persist in the final CAR T cell populations, including enhanced cytotoxicity in memory-derived cells and superior proliferative capacity in naïve-derived cells.

In CAR T cell therapy, a patient’s T cells are engineered to recognize and kill cancer cells. However, manufacturing involves strong stimulation of the T cell, raising questions about whether engineered T cells retain the differentiation states found intrinsically in T cells.

This publication encompasses the bulk of my PhD thesis work to understand how the ‘history’ of a T cell impacts anti-tumor functionality when the T cell is engineered to recognize and kill cancer cells with a synthetic receptor known as a chimeric antigen receptor (or CAR).

Antigen experience history directs distinct functional states of CD8+ CAR T cells during the antileukemia response - Nature Immunology 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...

I am thrilled to share my first-ever first author publication in Nature Immunology as my first post on Bluesky! Huge thanks to everyone who contributed to this work! See comments for more.

#celltherapy #immunology #immunotherapy #CARTcells

www.nature.com/articles/s41...