The ‘immunorevolution’ has begun at Penn

In Philadelphia, we’re used to revolutions. And all of us at Penn, said Robert Vonderheide, talking to a crowd of alumni on Saturday morning at Irvine Auditorium, “know one when we see one.” Of course, Vonderheide, director of the Abramson Cancer Center, was referring to the University’s very own “immunorevolution,” where Penn continues to lead the way—from conception to delivery in humans—in therapies that harness the body’s own immune system to fight cancer.

A panel, put together for Homecoming weekend and moderated by Vonderheide, featured several of Penn’s top experts in the immunotherapy field, including Carl June, the architect of the Kymriah chimeric antigen receptor (CAR) T-cell therapy; David Porter, the leading clinical investigator of the clinical trials that led to CAR T-cell approval; E. John Wherry, director of the Institute of Immunology and the newly named chair of the Systems Pharmacology and Translational Therapeutics department; Noelle Frey, the lead clinician treating patients with acute leukemia and chronic leukemia using CAR T-cell therapy; and Avery Posey, who, after completing his postdoctoral fellowship in June’s lab, started his own lab at Penn exploring the next generation of CAR T-cell therapy.

“The University of Pennsylvania is a bright institution, as you know, in the field of research, and Reuters ranked us as the fourth most innovative university in the world,” said J. Larry Jameson, executive vice president of the Health System and dean of the Perelman School of Medicine, during the event’s introduction. “We’ve been climbing that ranking, and today you’ll see just a few examples of how we earned that.”

The hourlong conversation flowed freely, touching first on the origins of Penn’s cell and gene therapy program, which was strategically created in the 1990s. Back then, when he was recruited to Penn, June was discussing with colleagues the novel, complex notion of taking a patient’s own T-cells, genetically modifying them in a lab, and then infusing them back into the patient with the expectation they’d boost the immune system and, ultimately, defeat the cancer.

What was unheard-of then has become a game changer, thanks to June and his team who were able to develop the gene therapy, test it with positive results for patients in clinical trials, and, just last year, receive FDA approval.

Feeding off this momentum, June said he thinks the principle behind the therapy, which has been OK’d to treat leukemia, a type of blood cancer, has been proven in a way that can work as a general solution for other cancers, including those involving solid tumors, as well as other diseases that involve a glitch in the immune system, such as multiple sclerosis.

“The issue is how long it will take,” said June, noting that he’s excited by the prospects. “We don’t know, but that’s what we are focused on.”

Wherry noted how Penn researchers’ pioneering work in figuring out how to “engineer cells and turn them into drugs” really speaks to how the immune system is becoming “one of the major toolkits in our ability to treat diseases.”

“This is different from the traditional way we think about drugs,” he explained. “This is a new concept in pharmacology and how you think about drug development.”

It’s been interesting for Frey to watch the shift in available treatment options for patients with leukemia over the years. “It’s night and day,” she said.

Frey cited a recent meeting she had with a leukemia patient in her 40s, who, before she came to Penn, was “running out of hope.” She had been treated with back-to-back therapies with no success.

“But, in my initial visit I had with her, I was able to give her three different potentially very effective strategies,” said Frey. A few years ago, that conversation would have been “dramatically different and disheartening,” she added.

The panel discussion also pinpointed the extreme importance Penn has placed on collaboration, specifically with colleagues at the School of Veterinary Medicine and the neighboring Children’s Hospital of Philadelphia, as well as with industry—to bring CAR T-cell therapy to fruition and then keep innovating.

Penn’s alliance with pharmaceutical company Novartis, for instance, was a model “that hadn’t been done before,” said Porter. “It’s a collaboration that allowed us to treat these patients and move this field forward at a pace that just wasn’t going to be possible [otherwise].”

At the end of the day, all the panelists’ work revolves around their patients—always. An interesting tidbit Posey shared was his personal experience getting to work closely with June.

“One thing I think is different about Carl is that, given his success, you would expect a different personality,” Posey said. “Carl is a very genuine person that tears up every time he discusses a patient, and that is something that will stick with me for the rest of my days. This is the reason we’re here.”

Questions from the audience members, many of whom were cancer survivors, varied widely. Talking cancer is never easy, and it’s sometimes hard to grasp, but one message rang clear—the attendees’ sincere gratitude to Penn’s cancer researchers and practitioners for giving them and their family members hope.

Vonderheide, touched by their sentiments, expressed his own “thank you” back.

“This is happening because we are a community,” he said. “Our patients are our dear friends, we treat them like family, and the rest of the Penn community has supported Penn Medicine and the Abramson Cancer Center in unbelievable ways. Almost every big idea that we’ve talked about today can trace back to a supporter and a scientist talking, where the supporter says, ‘Let’s get started today.’”

“The power of philanthropy is amazing, the power of this community is amazing,” he added. “No wonder we’re on the leading edge.”

Oluchi Okonkwo and Mitchelle Matesva, friends as undergrads who reunited a year after their graduation for Homecoming weekend, watched from the audience, in awe of their alma mater.

“It’s so amazing to see the kind of vision and innovation that’s going on at Penn,” said Okonkwo, a high school chemistry teacher in Hartford, Conn. “That’s why I came here. I’m so inspired.”

Norman Koven, a 1974 graduate of the College of Arts and Sciences, sang a similar tune, adding that as he battles advanced prostate cancer, “this is a key interest to me.”

“I hope I can benefit from one of these treatments in the future,” he said.

Source: penntoday.upenn.edu, by Lauren Hertzler