Is a cancer cure close? Researchers at Fred Hutchinson think so

Hopefully this breakthrough will come in time to help all those suffering from various Cancers. Enough of Cancer – its time to end its reign.

BY RON JUDD – Seattle Times  May 19, 2018 08:00 AM

“The microscopic particles that might change the world are being carted about on a medical campus near Seattle’s Lake Union.

The mode of transport: a plastic lunch cooler.

The little coolers are ubiquitous at the Fred Hutchinson Cancer Research Center, which four decades ago pioneered a groundbreaking treatment for blood cancers — the bone-marrow transplant, now an older science that still saves lives, but not without harrowing side effects.

Some new treatments — collectively, “immunotherapies” that unleash the body’s immune system to seek out and destroy cancer cells — have shown strong results in early testing on blood cancers.

In one ongoing trial, patients with a leukemia that had resisted previously known treatments achieved a remission rate of 93 percent — a result that even seasoned researchers at the Hutch called “astounding,” particularly given the treatment’s relative lack of the destructive side effects of traditional radiation and chemotherapy.

The weapon of choice was re-engineered human “CAR-T” cells, which did its work more efficiently and completely than even its creators had dared dream.

During that trial, the oncologist for s terminally ill patient phoned Dr. Stanley Riddell, a veteran Fred Hutchinson researcher, less than a week after the administration of a single dose of these super cells.

The stricken patient, plagued by pounds of malignant tumors in the lymph nodes of his neck, said he felt the deadly tumors “melting away like ice cubes.” The treatments are still being tweaked, but early results have left usually reserved researchers borderline giddy.

What’s next? Turning the same immunotherapy tech loose on other formerly incurable “solid tumor” cancers that long have ranked among medical science’s most-vexing killers.

A dozen trials are underway now at The Hutch and the affiliated Bezos Family Immunotherapy Clinic at Seattle Cancer Care Alliance for a broad range of blood cancers, lung cancer, breast cancer and melanoma.

A clinical trial for pancreatic cancer could start within the next year; an immunotherapy regimen for ovarian cancer is being tested, with promising initial results, on genetically altered mice.

The painstaking work to perfect the treatments clicks along one batch of supercharged cells at a time. Each batch winds up in an IV bag, carefully maintained and carried to patients at cold-beer temperatures.

Hence the armada of coolers, carried from a basement cell-production facility at The Hutch to the adjacent clinic, where a patient who as little as two years ago would have been without hope awaits a single-dose treatment that might prove miraculous.

THE TIME IS NOW

The promise shown in recent research has emboldened Fred Hutchinson leaders to proclaim, for the first time, that cures for a broad range of cancers are within sight. The time to make the last big leap, they say, is now.

Results from trials in the past two years make the leap from “progress” to “cure” less daunting, they say. And at The Hutch, one of a handful of institutions around the world conducting these experiments at an ongoing, intense level, the directive is coming from the top.

Hutch President Dr. Gary Gilliland, a veteran of cancer-treatment successes at Merck Research Laboratories, arrived at the Seattle nonprofit institution three years ago.

While on the faculty of Harvard, where he directed the leukemia program at Dana-Farber/Harvard Cancer Center, Gilliland proclaimed that “curative approaches” for most cancers were within sight by 2025.

“The reason I feel confident,” he said in an interview with The Times, “is that since we first said that three years ago, we’ve made extraordinary progress.”

By breaking down cancers and their immune-system combatants to their smallest, subcellular parts and learning how they get along — or preferably, do not — scientists at The Hutch and a handful of other leading research centers have proved they can eradicate cancer in some patients with a one-dose treatment engineered from the patient’s own immune system.

“We’re curing people,” Gilliland said. “The question is: Why aren’t we curing everybody, and how do we extend those curative methods to other types of cancers that have been more recalcitrant?”

SHOWING PROMISE

The Hutch has quietly expanded into a working cancer-killer campus with an ability to imagine, test, manufacture and deliver intensely personalized, lifesaving treatments to patients for whom all else has failed.

The advances are especially invigorating to its researchers because much of the new success is born of work conducted there for decades.

Immunotherapy, Gilliland said, is “built on the legacy” of The Hutch’s bone-marrow transplant techniques, pioneered by the late Dr. E. Donnall Thomas, a 1990 Nobel Laureate and his wife, Dottie.

The treatments provided the first proof that immune cells transplanted into the body could seek out and kill leukemia cells in humans. The focus since has shifted to encouraging immune cells in patients’ bodies to do the work, eliminating the need for matched donors of stem cells from bone marrow or blood.

A range of techniques has evolved.

The one showing promise in recent blood-cancer trials, the “CAR-T” treatment, is one of a handful of new “adoptive T-cell” techniques that have staved off cancer in many patients.

In this one, naturally occurring immune cells known as T cells are genetically engineered to produce new synthetic receptors, called chimeric antigen receptors, or CARs.

The end product — a souped-up CAR-T cell — can identify specific proteins, or antigens, on the surface of cancer cells. Multiplied in the laboratory and reintroduced to a patient’s blood stream, they target and kill those cells.

Another bonus: Adoptive T-cell treatments are considered a “living therapy” because immune systems trained to kill cancer might continue to do so, or even learn to get better at it over time.

Significant problems remain. CAR-T treatments’ side effects include neurotoxicity, which causes seizure-like symptoms, and another syndrome has caused dramatic drops in blood pressure.

But researchers say they are typical early-stage roadblocks that can be mitigated by improvements to treatment regimens, including controlling doses.

Cost is another factor: The highly individualized treatments in their current form are labor-intensive and expensive. The hope is that costs will drop as procedures are standardized.

The growing consensus among researchers is that CAR-T treatments, alone, will prove less effective against ubiquitous solid-tumor cancers. But most agree a combination of developing immunotherapies is the likely key to future cures.

“Now we can manipulate that immune system, we can genetically reprogram it and we can develop drugs that can activate it,” Gilliland said. “We have all the tools in our hands. It’s not a question of, ‘Can we?’ We can. The question is how we extend that to all patients.”

He acknowledges “pushback” on these proclamations from within the field. But he believes it’s important to create motivational pressure to finish the job.

“We’re not trying to overhype this, or promise something we can’t deliver on,” Gilliland said. “It’s our responsibility to make this happen. If we don’t, we have failed patients dying from cancer while we have this conversation.”

‘DR TCELL’

Most of those at The Hutch — longtime investigators with international reputations or undergrad lab assistants — have embraced Gilliland’s challenge.

Dr. Phil Greenberg is the head of Immunology at the Fred Hutchinson Cancer Research Center. Greenberg has been at The Hutch since 1976, and is an expert in discovering how the immune system can be manipulated to fight diseases such as the pancreatic cancer that claimed the life of his father in 2001. A legend in the field, he still enjoys the occasional, satisfying burp of the liquid nitrogen freezer.

Mike Siegel Seattle Times

Some of the most creative research occurs under Dr. Phil Greenberg, a 71-year-old optimist who has been chasing cancer cures at The Hutch since 1976. Greenberg wears his commitment on the license plate on his convertible: “DR TCELL.”

Greenberg’s lifetime fixation on besting cancer has become intensely personal. His father died in 2001 from pancreatic cancer, which stands as the third-largest cause of U.S. cancer deaths, and is increasing in numbers.

Greenberg’s team is exploring ways to equip immune cells with specific “T-cell receptors,” which can see antigens inside tumor cells (rather than surface antigens sought by CAR-T cells) to activate and unlock cellular doors to immune-system cancer destroyers.

Greenberg and his colleagues are fighting the immunotherapy battle against solid tumors via lab work so data-intensive that The Hutch has increasingly reached out for help from power-computing partners in Seattle’s tech sector.

Researchers credit such breakthroughs to The Hutch’s long-game approach to cancer science.

Providing that room to innovate, in a field where fierce competition for trial funding tends to work against longshot creativity, has been the key to long-term success at The Hutch, Greenberg said.

Dr. Kristin Anderson is conducting mouse trials for an immunotherapy treatment for ovarian cancer. It’s one of the deadliest forms of the disease because, by the time it is detected, the cancer usually is quite advanced. Fewer than half of diagnosed patients live beyond five years.

At that point, “There’s not really a lot you can do,” said Anderson, a breast-cancer survivor. “We’re hoping that immunotherapy can really push forward the bar and change some of those numbers so people really do have hope.”

FOOLING CANCER

Immunotherapy treatments for ovarian and pancreatic cancers are being prepped for clinical trials in Greenberg’s lab. His team has an idea of what to expect — thanks largely to a giant technological leap in a tiny host: the common laboratory mouse, genetically re-engineered.

By injecting altered DNA into mouse embryos, trial-ready mice can be produced much more quickly and “model” human treatment effects far more precisely, accelerating the pace of moving treatments from mouse study to human trial.

The detailed feedback they provide allows researchers to “leapfrog” obstacles, sometimes overcoming them before they are ever encountered in humans, Greenberg said.

“Every indication we have in the mouse model (for pancreatic cancer immunotherapy) has told us it will work,” he said. “It has also already told us about some of the obstacles we are likely to face for complete tumor eradication. We’re already building strategies to address that.”

Scientists long have known that cancer’s “success” rate has been aided by its ability to trick, or even spark a shutdown impulse in, immune cells preprogrammed to kill it. Researchers in Greenberg’s labs are working to block those processes — or perhaps even fool a cancer cell into believing it has shut down an immune response, when it has not.

Other experiments aim to retrain immune cells receiving a “suicide” signal from a tumor to not only ignore that impulse, but also kick into “attack” mode, instead, when receiving it.

The new technology provides instant feedback on the effect or failure of treatments that is so voluminous that other divisions at The Hutch are scurrying to devise software programs that can help analyze it.

“We have incredibly sophisticated ways to understand what our cells are doing in the patient,” Dr. Aude Chapuis said. Until recently, researchers could see, for example, that a cancer cell was able to evade the grip of an immune T cell. Now they can see why.

“It’s sort of like going from a two-dimensional black-and-white picture to a 3D movie,” she said.

FUNDING CHOKEPOINT

Though the cancer fighters see the likely pathway to cures for a full range of cancers it remains blocked by the chokepoint of research funding, which has not advanced at the same rate as the science.

About 70 percent of The Hutch’s $550 million annual budget comes from grants and contracts, largely through the National Institutes of Health. The funding got a $3 billion (8.3 percent) boost this year but still lags behind inflation over the past decade and a half.

Scientific advances have created “unparalleled opportunity,” said Greenberg, who has spent many days lobbying congressional committees. “But the resources to actually use them, or use them broadly, is really limited. And that’s ridiculous.”

Some local donors have stepped up: The Bezos family recently made a $35 million donation. But realizing the potential of the science in short order will require “new dollars” beyond the dwindling slice of federal discretionary spending, which often pits cancer research against other worthy social needs, The Hutch leaders say.

Among cancer patients, “The hope is that it’s possible, it’s real, it’s not a pipe dream, and it can happen,” said former Gov. Christine Gregoire, a cancer survivor who since 2016 has chaired the center’s board of directors.

“But the idea that we can get there from here relying solely on NIH funding isn’t possible. The only thing in my mind that stands between us and the cure for cancer is funding. We’ve got to find another way.”

Seattle, Gregoire noted, might be uniquely blessed with the ingredients needed to turn potential to reality. Literally within sight of The Hutch campus are the trappings of big data, digital technology, higher education, biotech and other potential elements of the cure. And mind-boggling reserves of private money sit in bank accounts.

Gregoire and Gilliland hope the Bezos gift becomes an example because competition for federal funding — of which The Hutch has long won a lion’s share — is increasing. More than 90 percent of federal research grant requests are rejected, and one of those, Gilliland believes, might contain cancer’s lethal bullet.

He points to recent successful CAR-T treatments, which, 20 years ago, surely would have earned a “REJECT” stamp.

“People would have thought that was just nuts,” he said. “The most important advances are driven by innovation. And we learn by tech partners like Amazon that you don’t want to be afraid to fail.”

The money, the technology, the expertise and the will are here, Gregoire believes.

“We have a whole lot of work to do,” she said. “But Seattle really could be the place in the world where cancer is cured.”

Dr. Phil Greenberg is the head of Immunology at the Fred Hutchinson Cancer Research Center. Greenberg has been at The Hutch since 1976, and is an expert in discovering how the immune system can be manipulated to fight diseases such as the pancreatic cancer that claimed the life of his father in 2001. A legend in the field, he still enjoys the occasional, satisfying burp of the liquid nitrogen freezer. Mike Siegel Seattle Times”

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