Much of the world, including research at Penn Medicine, has focused its attention on how T cells — which play a central role in immune response — might shape the trajectory of COVID-19 infection, and how immunotherapy can shed light on treatment of the disease.

Already a leader in immunotherapy research and treatment, Penn Medicine pioneered the groundbreaking development of CAR T cell cancer therapy. Avery Posey, Jr., PhD, an assistant professor of Systems Pharmacology and Translational Therapeutics, trained as a postdoctoral fellow in the lab of Carl June, MD, a professor of Pathology and Laboratory Medicine and director of the Center for Cellular Immunotherapies in the Abramson Cancer Center, who pioneered CAR T cell immunotherapy to treat cancer. Now as a faculty member at Penn, Posey has maintained a focus on T cell therapeutics, mostly for the treatment of cancer.

“I talk to people on airplanes, online in video games, in coffee shops, really everywhere, who talk about either their personal experiences fighting cancer or the experiences of their loved ones,” he said. “Fighting cancer is a team effort and it's hard on everyone. I want my lab's research to discover treatments that increase the effectiveness, decrease the side effects, and uphold the dignity of those fighting.”

Posey lost a cousin in 2019 to stage 4 pancreatic cancer and he has an aunt currently fighting the same disease. He said there aren't many therapeutic options for cancers that advance to that stage. His goal is to work to discover better treatments until eventually cancer can be controlled as effectively as the chickenpox or measles, with a preventative vaccine.

In the Q&A below, Posey discusses how he hopes to leave an indelible mark on the world through scientific investigation.

Briefly describe your background and what inspired you to do this research.

I hold two bachelor of science degrees (Bioinformatics & Biochemistry) from the University of Maryland, Baltimore County (UMBC) and a PhD in Genetics from the University of Chicago. Now as an assistant professor of Systems Pharmacology and Translational Therapeutics, my lab develops engineered T cell therapeutics, mostly for cancer treatment, with a focus on glycosylation (the process where glycans — carbohydrates involved in inflammation — attach to proteins) changes that occur in cancerous tissues.

This research combines two of my biggest interests — the use of gene therapy to treat disease and the investigation of little known biology, such as the roles of glycans in cell behavior. The pursuit of new knowledge, the roads less traveled — those are my inspirations.

What research are you currently undertaking?

We have developed a T cell therapy that genetically engineers a patient’s own immune cells to recognize an antigen called Tn-MUC1. Tn-MUC1 is commonly found on the surface of tumor cells, never or rarely found on normal tissues, and represents a change in glycosylation that tumors undergo. This therapeutic is now under clinical investigation in a phase I trial by Tmunity Therapeutics.

My laboratory is working diligently to identify ways we can enhance this particular therapeutic as well as identify other proteins with altered glycosylation in tumor cells in order to build new therapies. Recently, we found that by modifying the signaling domain of a chimeric antigen receptor (CAR), we can enhance the anti-tumor response of these engineered T cell therapies.

What are the biggest challenges you face as a scientist and where do you see the greatest opportunities? 

Science moves at incredible speeds, yet the structures that support the science are unbearably slow. When writing grants to support new science, grant reviewers often seek assurances that the project will work and that funding such work is low risk. That means investigators are often finishing entire projects before being funded to do that (now complete) proposed work.

But scientific breakthroughs do not arise from low risk studies. There is a great need for funding high-risk research, where ideas are the most important part of a proposal and not preliminary data. With a one-to-two year lag on receiving government funding through the types of grants I mention above, funding does not keep pace with the science.

I think this is an excellent opportunity for philanthropic organizations and industry collaborations to support high-risk research and create more scientific breakthroughs, such as next-generation CAR-T cell therapies for solid tumors.

Source: University of Pennsylvania