What's Next in CAR T-Cell Therapy?

CAR T-CELL THERAPY AND THE FUTURE OF MEDICINE WITH BRUCE LEVINE

The future of medicine is one where all cancers are either 100% curable or turned into manageable diseases. You’ve heard me tell the story in my keynotes for many years. Now it’s time for you to hear from one of the heroes of that story, Bruce Levine.

Bruce and his colleagues pioneered CAR T-cell therapy, one of the most important breakthroughs in the history of medicine, where your own immune cells are reprogrammed to attack and destroy your cancer. They developed it, applied it, saved the first lives, achieved the first FDA approvals, and perfected a therapy that has now been applied to tens of thousands of patients around the world and will soon be hundreds of thousands.

Now Bruce is targeting solid tumors. And he’s moving CAR T-cell production INSIDE the human body to slash the costs. And he’s not stopping at cancer …

Which makes CAR T-cell therapy not only one of the most important breakthroughs in the history of medicine, but also one of the most important platforms for the FUTURE of medicine.

MEETING BRUCE LEVINE

I met Bruce Levine and his colleague Don Siegel when they generously showed me and some of the Emily Whitehead Foundation board members around the Centre for Cellular Immunotherapies at the University of Pennsylvania. 

The introduction came through the remarkable Tom Whitehead. I’ve told the Tom, Emily and Kari Whitehead story on stage for almost a decade and I recorded a quick summary version here, after we met and presented at the same speaking gig last year. Tom’s brave daughter, Emily, was the world’s first paediatric patient for CAR T-Cell therapy, which cured her of acute lymphoblastic leukaemia, at the age of seven. Tom and his family have worked tirelessly ever since, through the Emily Whitehead Foundation, to connect other children with the same life-saving therapies. If that wasn’t enough, Tom he still works as a linesman repairing power lines in all weathers across Pennsylvania. A true hero, and I’m proud to know him and call him a friend. 

And Emily was, of course, Bruce’s patient. Bruce and his colleagues, including Professor Carl June and Dr Stephan Grupp and Professor Don Siegel, saved her life. (Bruce stands on the right in the above photograph, Don is next to me in the white coat, and Tom is on the left).

Today, Bruce is the Barbara and Edward Netter Professor in Cancer Gene Therapy at the University of Pennsylvania’s Perelman School of Medicine, as well as the Deputy Director - Technology Innovation and Assessment for their Center for Cellular Immunotherapies and the Founding Director of their Clinical Cell and Vaccine Production Facility. 

More than that, I can tell you he’s a great scientist and a wonderful human being who truly, truly cares about his patients.

Bruce was humble and quietly spoken, and he answered all my questions with patience and good humor, taking care to formulate his responses so I had no trouble understanding the science – qualities that shine through on the podcast. He was doubly generous in making time for our interview, as he was convalescing from a painful knee injury and subsequent surgery, which placed all kinds of additional pressures on his work schedule.

This podcast has everything – story, emotion, and a window into the astonishing near future of medicine. I know you’ll enjoy it!

CHECK OUT THE PODCAST TRANSCRIPT →

PASSION, SERENDIPITY AND A CRITICAL DECISION

I love how his story started at UPenn and Children's Hospital of Philadelphia, his career brought him back there, and how he and his colleagues saved Emily Whitehead’s life there, and now Emily is started as an undergrad there as well,living in a dorm that is literally 100 meters from Bruce’s freshman dorm! If synergies exist in this universe, there they be! As I said on the podcast, if someone was writing this is a movie script, no one would believe it. 

Also fascinating was the zig-zag from clinical work to science then back to the translational side, inspired by his daily encounters with paediatric patients in need. So often it seems, the truly ground-breaking innovations (which inevitably require many years of effort and dedication) only come when changemakers connect with their true passions. 

Also remarkable was the role of serendipity in identifying a drug to arrest Emily’s potentially fatal cytokine release syndrome, all of which had to be done ‘in the moment’ and under extreme pressure, and how that drug went on to become the FDA-approved co-label with CAR T-cell therapy.

30,000 LIVES AND ONLY THE BEGINNING

The numbers say it all: in the 11 years since saving Emily’s life, paediatric patient #1, the therapy Bruce and his colleagues developed has been used to treat almost 30,000 patients (children and adults) around the world. Now THAT is what I call a game-changer.

Astonishing as the impact has been, there is more to come. Much more.

THE FUTURE #1: TARGETING SOLID TUMORS

One of the biggest future frontiers is adapting CAR T-Cell therapies from blood cancers to successfully target solid tumors, such as those associated with pancreatic, breast and lung cancer. It’s a complex and multifaceted challenge (in terms of immunosuppression, finding the right target that is only expressed on a solid tumor, and getting access to the cancer cells) but we ARE making steady progress and Bruce speaks confidently about making the transition, pointing to an exciting trial that is direct-injecting CAR T-cells to treat glioblastoma, a particularly aggressive form of brain cancer, as an example of the progress being made.

See also my interview with Ben Stanger in “Three New Frontiers In Cancer Medicine” for more on challenges and progress in targeting solid tumors.

HOW TO SLASH COST AND COMPLEXITY?

Bruce pointed out that globally, only 20 or 30 percent of patients that could receive CAR T-cell therapy actually do. This is down to approvals, education, getting frontline family clinicians to understand this is an option for their patients, and cost.

A core task for Bruce and his colleagues, and one of the pathways they are working on to create a MUCH better future, is reducing the complexity and resourcing requirements for manufacturing the engineered T-cells. As he put it, “When we have an approval in solid cancers, then you multiply the number of patients that could be eligible by 10, and then we get into the problems of scale, because these are complex to manufacture outside of the body. We need expensive reagents and materials and equipment. We need labor, and I've said that there aren't enough humans on earth when we have an approval in solid cancers.”

That’s why they’re moving manufacturing INSIDE the human body.

THE FUTURE #2: MOVING DRUG MANUFACTURING INSIDE THE BODY

Bruce and his colleagues are working on using messenger RNA that is coded for chimeric antigen receptor (just as COVID vaccines use mRNA coded to instruct cells to make spike proteins). The coded mRNA is contained in lipid nanoparticles coated with an antibody that directs them to T-cells where they harness the natural protein manufacturing capabilities of the body for in-vivo CAR T-cell production. The result: no more waiting for T-cells to be removed and manufactured in the lab and returned via infusion. Indeed, the complete elimination of external cell manufacturing – with a MASSIVE commensurate reduction in cost!

All of this was beyond what Bruce thought possible 4 years ago. Now it’s in preclinical stages. Wow. 

But if that isn’t enough to excite you …

THE FUTURE #3: IN VIVO DRUGS FOR MANY DISEASES

Question: If you can instruct the body to manufacture its own specially-programmed CAR T-Cells, why stop there? Why even stop at cancer? 

Answer: We won’t. 

As Bruce points out, the future is much richer and more exciting again, because we’ll be using CAR T-Cells to target autoimmune diseases such as lupus, and we’ll be programming our bodies to manufacture other drugs (not CAR T-cells) to defeat sickle cell disease and HIV and viral infections contracted after stem-cell transplants and many, many more non-oncologic diseases.

Oh, and that’s before we use the same methods to administer preventers for diseases which show up as high-risk in genetic tests.

To quote Bruce verbatim: “Think of the power of this genetic technology. If you have a target, then you can target an immune cell against that target. And it doesn't have to be a chimeric antigen receptor when you're thinking about immune cells. Think of these cells as drug factories. You could use them to deliver other drugs.” 

Programmable medicines. We’ve talked about them before. Bruce and his colleagues are delivering up a bunch of new flavors. 

For an excellent paper canvassing some of the opportunities ahead, see CAR-Based Therapies: Opportunities For Immuno-Medicine Beyond Cancer, published in Nature Metabolism.

FURTHER INSPIRATION

How are you feeling now, about the future of medicine? Optimistic? Excited? You should be! If you need further inspiration, listen to my interview with Kiran Musunuru on Gene Therapies to Prevent Heart Disease or my soon-to-be published interview with George Church on gene therapies to extend lifespans, or maybe subscribe to FutureBites on your favorite podcast platform so you don’t miss any of our interviews with future-makers. 

Or hey, why not book me to deliver a high-energy inspirational keynote at your next event? Then I can meet you and your colleagues and together we can explore all kinds of pathways to a better future!

Cover image credit: “Two girls with acute lymphocytic leukemia receiving chemotherapy” Bill Branson & National Cancer Institute