In biotech, where everything is uncertain, execs like to be as predictable as possible. Scripts are maintained, nasty surprises are avoided whenever possible and speed is fine, so long as you stick to your schedule and don’t look like you’re in too much of a hurry.
And then there’s Sean Parker. Parker had an easy role to play as the billionaire founder of a new cancer R&D institute. The trailblazers could get a fresh source of cash and a few years from now he could claim progress on the ever-popular notion of finding a cure for cancer.
Parker, a central figure in this generation’s social media revolution, clearly had a more disruptive plan in mind.
On Monday evening, the University of Pennsylvania and the Parker Institute confirmed the news that Antonio Regalado at MIT Technology Review had broken earlier in the day: Parker is bankrolling a surprise move by Penn’s legendary Carl June and some of his colleagues to do the first gene editing experiment in humans using CRISPR-Cas9, a new technology that has been heralded as a simple, effective tool for slicing and dicing DNA.
They’re looking to use it on improving adoptive cell therapies for cancer, one of the hottest fields in immuno-oncology research.
“The study, an open label, Phase I trial which will examine safety and manufacturing feasibility of autologous T cells engineered to express NY-ESO-1 TCR and gene edited to eliminate endogenous TCR and PD-1, will build on Penn’s progress investigating other types of personalized T cell therapies for cancer, including both chimeric antigen receptor (CAR) T cells and NY-ESO-1 transgenic T cells,” Penn said in a statement to ENDPOINTS. “The study is designed to test the hypotheses that checkpoint resistant T cells may be safe and have improved antitumor activity. The pilot trial will enroll patients with multiple myeloma, melanoma and sarcoma at Penn’s Abramson Cancer Center and two other academic centers. Funding for the trial has been provided by the Parker Institute for Cancer Immunotherapy.”
Part of the purpose of the study, noted Parker’s institute in a followup message, is to unleash “the power of the T-cell while simultaneously reducing the chance for autoimmunity.”
Penn’s team presented their study to an NIH safety board Tuesday morning, outlining plans to recruit 18 patients: 6 patients with myeloma, 6 with sarcoma and 6 with melanoma.
These patients will be selected by their expression of the antigen NY-ESO, with researchers at Penn, MD Anderson and UC San Francisco all participating. Using CRISPR, they plan to disrupt expression of endogenous TCR and PD-1, which may increase the persistence of these cells, increasing the safety and efficacy of the treatment. Targeting PD-1, they believe, should create “checkpoint” resistant T cells, improving proliferation of the cells.
Initially, they expect to try this on three patients over 4 weeks, then check and see if there are any unexpected safety issues. If there aren’t any, then they’ll go ahead with the rest of the patients.
One of the greatest risks associated with CAR-Ts has been cytokine release syndrome, or cytokine storm. The investigators noted that there’s a well-established protocol for tracking this threat and recruiting patients that are less likely to be killed by it. And the researchers also want to see just how feasible it will be to manufacture this CRISPR-edited therapy.
Panel member Laurie Zoloth pressed June and his colleagues about the financial implications of the study. Novartis has played a major role in funding Penn’s CAR-T work, adapting cells with a chimeric antigen receptor to target them against cancer cells. But June noted that this isn’t a CAR, it’s a gene edited cell which “has no relationship with Novartis.”
Panel members also advised the Penn team to highlight the pioneering aspect of the trial as the first ever use of CRISPR in humans to any patients before they sign on. And at about noon they voted unanimously – with one abstention – to approve the trial.
Coming up with a better, safer way to spur a T cell attack on cancer has become one of the Holy Grails of biotech. But it wasn’t supposed to play out this way in gene editing.
There are several biotechs looking to use gene editing tech in cancer. Editas, which took an early lead on CRISPR-Cas9, was also widely billed as the one that would likely be the first to use it in human studies. And Cellectis has been using TALENS in an effort to prove that its precocious CEO Andre Choulika has a better technology for the job.
Parker, though, seems intent on tearing up a carefully arranged stage. From his start with Napster, which got him in trouble with the feds even as it pointed him down the road to Facebook fame and fortune, Parker enjoyed the disruption — changing the music industry and the way people communicate in ever growing networks.
Now he’s found a way to adopt a similar role in cancer R&D. And everyone will be watching to see what he comes up with next.
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John Carroll, Editor and Co-Founder
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