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Brainstorm Health: Nobel Prizer Winners, CAR-T Glitch, Pfizer’s Next CEO

Happy Monday. The 2018 Nobel Prize in Physiology or Medicine was awarded today to James P. Allison and Tasuku Honjo for groundbreaking discoveries that have led to a genuine revolution in cancer therapy—techniques that harness the human immune system to fight this family of diseases. It is a damn good choice.

To understand why, it helps to consider one of the central and enduring mysteries of cancer: It’s a pathology that comes from within. The disruption and destruction of healthy tissue by malignant cells is a homegrown terror, a proliferation of biological anarchists that were born and bred and ultimately corrupted within the human organism. It is not, like so many of the diseases we think of when we think of “disease,” a threat from outside the body—a raging infection like influenza, pneumonia, TB, or Ebola.

That quality of “selfness”—that eerie likeness in façade, in many ways, between invader and invaded—has arguably been the single largest impediment to treating and preventing cancer.

But the story is a lot more complicated than that. That’s because, in spite of this ability to blend in with the normal, cancer cells are often caught and killed by our remarkably vigilant immune system, which manages to recognize certain key markers, or antigens, on their cell surfaces that identify them as not-quite-right.

So why, you ask, are cancer cells “often” caught, but not caught all the time? Why do immune sentries often—and even routinely—find and destroy these bioterrorists, but sometimes fail with deadly consequence?

That’s where Allison and Honjo come in.

For much of the past century and longer, research scientists and clinical experimenters focused their efforts on trying to rev up the immune systems of cancer patients, believing that that’s where the failure lay. As Allison told me in an on-stage interview two years ago: “In the early days, people just tried to turn [the immune system] on, to pour more gas in it, to push harder on the pedal—without really knowing how it worked. What really broke it open was we realized there’s more than just turning it on. There’s actually a very complex system of off-switches, brakes, to keep it from killing you—because it will if it’s unrestrained. We found a way to do that temporarily, to unleash it to attack cancer cells.”

As it turns out, cancer can trip up the body’s bodyguards in a number of ways—but one particularly insidious trick is to send out signals to immune system regulators to hold back on an attack. In short, they induce the guards to look the other way.

When Jim Allison suggested that hypothesis, the mandarins of the cancer research establishment scoffed—or worse, ignored him. Still, he pressed on. Working out of the University of California, Berkeley, in the 1990s, Allison (who’s now at Houston’s MD Anderson Cancer Center and a seminal force within an exciting collaboration called the Parker Institute for Cancer Immunotherapy), figured out how one such “off” switch, or “immune checkpoint,” known as CTLA-4, could be flipped to preempt an attack by immune defenders called T cells.

What’s more, he went on to develop a molecule that could release this emergency brake, allowing the T cells to, at last, seek and destroy their quarry. (Read Erika Fry’s terrific 2014 feature story on this in Fortune.)

Working in parallel at Kyoto University in Japan, Honjo helped elucidate how a different immune checkpoint, called PD-1, put the brakes on T cells. (You can read the press release for the Nobel Prize announcement here.)

Many dozens of anti-cancer therapies have been developed targeting PD-1 and a related molecules in the same pathway. So far, as I’ve written, such therapies have led to spectacular and unprecedented remissions in a subset of patients with certain types of advanced cancer, but have fallen far short of that goal in most patients. The treatments have also come, in some cases, with serious side effects and complications.

But the hope is, the age of cancer immunotherapy is just beginning and we are finding more and more clues to this puzzle every day.

You can thank scientists like Jim Allison and Tasuku Honjo for that.

On a separate front, I’m moderating two roundtable dinners later this month (one in New York and one in Palo Alto) for senior leaders who are interested in artificial intelligence and how it’s impacting business.

To apply for a complimentary seat, click here:

Clifton Leaf, Editor in Chief, FORTUNE


A rare CAR-T manufacturing glitch raises concerns. CAR-T technology, which, in short, has made it possible to re-engineer human immune cells to become targeted cancer killers, has made waves in the life sciences. But a new study serves as a reminder that new technologies come with potential problems that must be addressed. In this case, University of Pennsylvania researchers said that a single leukemia cell got mixed in with a batch of a patient’s modified immune cells being grown for a CAR-T therapy. The result? The leukemia cell became resistant to the CAR-T treatment and led to an ultimately deadly relapse in the patient during a clinical trial. (Reuters)


Pfizer’s CEO is stepping aside with a successor in mind. Longtime Pfizer CEO Ian Read will step down from his executive perch on January 1, the company announced Monday. Read will transition into an executive chairman role. Pfizer has already named his successor, too—Dr. Albert Bourla, who is the current chief operating officer of the drug maker. (Fortune)

China’s fledgling biotech scene. I spoke with biotech investor (and cancer immunotherapy) extraordinaire Brad Loncar about the tailwinds, and headwinds, affecting China’s nascent biotech stock scene. As Loncar tells me, there’s plenty of reason for investor optimism given the regulatory changes the Chinese government has been pursuing to prop up the industry; but there are also plenty of growing pains, including those tied to poor performance by recent IPOs and a vaccine scandal. (Fortune)


Updated flu death numbers paint a dark picture. The latest report from the Centers for Disease Control (CDC) find that more than 80,000 Americans died from the flu last winter, setting a decade-long record. We’ve known for a while now that the toll would be concerning; but perhaps the most concerning part is the number of young children and teens who died in the outbreak last year—180, which is an all-time high since the CDC began collecting this data with modern disease surveillance methods. (New York Times)


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Produced by Sy Mukherjee

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