Discover and Develop Novel Checkpoint Inhibitors
PD-1 is a critical inhibitory checkpoint for T cells, and antibodies that block its signaling in turn promote the immune-mediated clearance of malignant cells. Unfortunately, current anti-PD-1 therapeutic agents benefit only a small fraction of patients. Thus, the need to develop additional additional therapeutics targets remains urgent.
![Schematic showing model of targeting PAG using anti-PAG antibodies.](https://www.rheumatologyatcolumbia.org/sites/default/files/styles/cola_media_200/public/media/images/2021-12/pag.jpg?itok=z_v0E1ea 200w, https://www.rheumatologyatcolumbia.org/sites/default/files/styles/cola_media_260/public/media/images/2021-12/pag.jpg?itok=RU5NsUWe 260w, https://www.rheumatologyatcolumbia.org/sites/default/files/styles/cola_media_320/public/media/images/2021-12/pag.jpg?itok=ImmSUuyt 320w, https://www.rheumatologyatcolumbia.org/sites/default/files/styles/cola_media_400/public/media/images/2021-12/pag.jpg?itok=zLYBVZaW 400w, https://www.rheumatologyatcolumbia.org/sites/default/files/styles/cola_media_520/public/media/images/2021-12/pag.jpg?itok=lu8SUXkV 520w, https://www.rheumatologyatcolumbia.org/sites/default/files/styles/cola_media_640/public/media/images/2021-12/pag.jpg?itok=BPHJl1bk 640w, https://www.rheumatologyatcolumbia.org/sites/default/files/styles/cola_media_800/public/media/images/2021-12/pag.jpg?itok=P8PC7aDR 800w, https://www.rheumatologyatcolumbia.org/sites/default/files/styles/cola_media_1040/public/media/images/2021-12/pag.jpg?itok=JgZ3kRgt 1040w, https://www.rheumatologyatcolumbia.org/sites/default/files/styles/cola_media_1600/public/media/images/2021-12/pag.jpg?itok=mE4jIkBY 1200w, https://www.rheumatologyatcolumbia.org/sites/default/files/styles/cola_media_1280/public/media/images/2021-12/pag.jpg?itok=ardTU9sV 1280w)
Schematic showing model of targeting PAG using anti-PAG antibodies.
Making use of high-resolution proteomic approaches, we have uncovered targetable signaling proteins downstream of PD-1, as well as novel checkpoints that are highly expressed on tumor-infiltrating lymphocytes. In accordance with these discoveries, our current goal is to further develop our understanding of the biology of these proteins, and to confirm their value as potential therapeutic targets.