Patrick Hwu: How does anti-CTLA-4 and anti-PD-1 combination work mechanistically?

Patrick Hwu shared a post on LinkedIn:

“The combination of anti-CTLA-4 and anti-PD-1 antibodies is FDA approved for the treatment of advanced melanoma.

How does this combination work mechanistically?

In a recently published study in Cell by Cell Press using both single cell TCR and RNA sequencing, Wang et al demonstrate that the combination results in higher numbers of clonal T cells capable of recognizing melanoma and that anti-CTLA-4 drives the expansion of exhausted T cells while anti-PD-1 reinvigorates them.

These insights may help with future patient selection as well as enhanced combinations and treatment schedules.”

Source: Patrick Hwu/LinkedIn

Combination anti-PD-1 and anti-CTLA-4 therapy generates waves of clonal responses that include progenitor-exhausted CD8⁺ T cells.

Authors: Kevin Wang, Paulina Coutifaris, David Brocks, Guanning Wang, Tarek Azar, Sabrina Solis, Ajeya Nandi, Shaneaka Anderson, Nicholas Han, Sasikanth Manne, Evgeny Kiner, Chirag Sachar, Minke Lucas, Sangeeth George, Patrick K. Yan, Melanie W. Kier, Amy I. Laughlin, Shawn Kothari, Josephine Giles, Divij Mathew, Reem Ghinnagow, Cecile Alanio, Ahron Flowers, Wei Xu, Daniel J. Tenney, Xiaowei Xu, Ravi K. Amaravadi, Giorgos C. Karakousis, Lynn M. Schuchter, Marcus Buggert, Derek Oldridge, Andy J. Minn, Christian Blank, Jeffrey S. Weber, Tara C. Mitchell, Michael D. Farwell, Ramin S. Herati, and Alexander C. Huang.

Patrick Hwu, MD, currently serves as the President and CEO of Moffitt Cancer Center. With a focus on understanding the dynamics between tumors and the immune system, Dr. Hwu’s research has been pivotal in advancing gene-modified T cell therapy.

He notably contributed seminal work on the development of the first chimeric antigen receptor aimed at combating cancer. His research portfolio extends to vaccines, adoptive T-cell therapies, and mechanisms of immune resistance.