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CAR-T pioneer on riding the NIH roller coaster, speaking up for science, and his funder Sean Parker

Dr. Carl June, introduced as “the cancer slayer” at an immunotherapy conference here, challenged scientists to be far more aggressive about pushing their perspectives in the White House and Congress.

What would he tell President Trump in the Oval Office? “Listen to scientists,’’ he said.

At the opening of the CAR-TCR summit Wednesday, June said, “I think we need to be vocal. I think, unfortunately, scientists have not been very good at making their case.” He lamented that the public hears scientists talk about global warming but little else, and described how his late wife’s cancer diagnosis put him on a mission to take on cancer.

June’s academic lab developed the science behind the first CAR-T approved by the Food and Drug Administration in 2017, which the University of Pennsylvania licensed to Novartis. Over the last decade CAR-T, other T cell receptor therapies, and checkpoint inhibitors — collectively known as cancer immunotherapies — have turned the field around from the days when June couldn’t win grant funding for his work.

“CAR-T is a process, not a drug,” he said. “This is really the first example of a long-term living drug.”

June is still following “patient 1” and “patient 2” from the first clinical trial of CAR-T launched in his Penn lab in 2010. He is a scientific adviser to Tmunity, a startup spun out of his lab, and he still collaborates with Novartis. His biggest funder is Silicon Valley tech mogul Sean Parker, whom he calls “amazing.”

June answered questions from STAT Executive Editor Rick Berke. A condensed and lightly edited version of their conversation follows.

Did your mission to fight cancer stem from your own personal tragedy with the death of your wife from cancer?

I initially went into science studying T cell biology and biochemistry. We never did a clinical trial until my wife got sick in 1996. She was 41 years old with ovarian cancer. I was a leukemia doctor and I saw what it was like being on the other side of the bed. It was awful.

With my colleagues in the lab, we tried several vaccines. I think it prolonged her life, but what I found out is how hard it is to do a pilot trial. Most of the expertise to open trials is in biotech and pharma, not in academia.

In the past you were denied funding for your research.

Basically, cancer had given up on the idea of immunotherapy with the exception of Steven Rosenberg at NIH, where he didn’t really have to get peer-reviewed grants.

All of us — the people at Fred Hutch, Memorial Sloan Kettering, MD Anderson, or Penn — were barely able to tread water. The peer review system said no. The immune system was not really studied by cancer biologists. They were reviewing our grants and they couldn’t then appreciate the nuances of why one immune system approach might be better than another.

Our first trials in CAR-T cells were actually in HIV. We were able to get continuous funding from NIAID, from infectious disease and HIV groups at NIH. It was only after CAR-T had worked in cancer cells that we could get funded from NCI.

Is there anything you’d like NIH to do now to get these therapies better funded?

You need to have adequate funding. NIH has been on a roller coaster for seven or eight years. Study sections (that evaluate grant applications) become much more risk-averse when money’s very limited, so they don’t take a chance on ideas that might be high impact, high risk, high gain. I think this is something we need to push on. Innovation will happen that way. And then things will transfer out into industry.

The administration has picked a new science adviser. Are you newly confident that there’s support for science and research, or are you concerned?

I’m concerned. I think we need to be vocal. I think unfortunately scientists have not been very good at basically making the case.

The actual huge breakthrough really was human genome sequencing, and that didn’t matter to the bottom line of research priorities [in Congress]. They couldn’t understand the implications of that. Now that they see those new innovative therapies being developed, I think it’s going to be an easier case on both sides of the aisle.

You’re sitting down in the Oval Office. What would you tell the president he needs to do?

Listen to scientists.

Science needs to enlist the public. CAR-T is a complex process and many scientists really didn’t understand it [at first]. The lay public was completely bewildered. Now they’ve actually embraced this. Patients are asking for this to be moved earlier upstream [in treatment].

Talk about your struggles getting industry on board.

In 2010, there was one approved cell therapy for cancer and that was the Dendreon autologous dendritic cell vaccine for prostate cancer. It gave a four-month life extension compared to Taxotere in metastatic prostate cancer.

It basically has been a commercial failure, so cell therapy was a hard sell and a complex process. It’s amazing how there was truly a tipping point; we went from no one said it could work to everyone said, yeah, it does work. An industry has emerged, which is really exciting.

But there may not be the infrastructure to do what needs to be done. How do you overcome that?

Normally when pharma is developing a new therapy, they develop [drugs] in sync with the manufacturing, and trials come online at the same time. When Novartis licensed the CAR-T from us in 2012, it was ready to go, we had data, but there was zero preparation for manufacturing. They were in catchup mode compared to where the clinical trials were. All the trials had happened in academia.

Now there is large investment that is going to remedy this. It is a complex process, not different from initially making computers, which is very difficult on a one-by-one basis. We need automated manufacturing, and industry can solve this.

Your biggest outside funder is Sean Parker?

Sean Parker has been an early believer. He’s a disruptor. He did Spotify, he did Napster. He put $600 million into a foundation and he’s 35 years old. The guy is amazing.

How much of the $600 million do you get?

I can’t say, but he gave equally. Approximately $25 million. There are six primary Parker Institutes with the idea we can leverage the infrastructure of different existing universities and then work on new therapies more nimbly than each of us in our own foxholes.

How did you meet? Did he call you?

He had seen through Stand Up to Cancer Sherry Lansing’s battle with breast cancer. He funded personally a private immune therapy for her and he became knowledgeable. He never went to college but he started reading. He reads Cell and all the Nature [journals]. He became interested in immune therapy and could he hack the system and make it work more rapidly? That’s how I met him, when he was looking into how to make this happen faster.

How deep does he go? Have you, the world expert, learned anything from him?

Oh, sure. He’s very opinionated, as all smart people are. We’ve stayed up all night talking about different approaches to make things happen.

CAR-T is seen as a niche therapy in some quarters. What needs to happen for this to become more mainstream?

The ultimate cost of cancer will go down if we have curative therapies. Right now the cost is going up because people live longer and we’ve gotten really good at heart disease so there’s an epidemic of cancer. It costs more now to treat it because we have a lot of therapies that make it into a chronic disease rather than a cure.

That’s gonna be expensive unless we can add a curative therapy. We need to get past an inflection point and costs will go down.

You sound optimistic about the future.

Oh, yeah. There’s not a cancer that’s been discovered where I don’t think there’s going to be a immune solution.

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