Science on the horizon

Fred Hutch immunotherapy researcher Dr. Jordan Gauthier predicts that new data will be released in 2020 on combination immunotherapies that will steer the field toward its future. The idea is that the synergy between two treatments with different mechanisms should make it tougher for cancer to shut down the killing response.

“Many trials are ongoing, but we will start seeing results,” Gauthier said.

Further improvements in immunotherapy will come from deep analyses of patient samples and data to learn how a treatment went right — or wrong — and using that information to make better ones. New technologies have the power to help scientists do just that, and 2020 will bring further progress in this area, said computational biologist Dr. Raphael Gottardo, thanks to growing capabilities to make sense of the heaps of data that in-depth analytical methods generate.

“We will continue making good progress on using data science to understand mechanisms of response and/or relapse in immunotherapy,” said Gottardo, who is the scientific director of the Hutch’s Translational Data Science Integrated Research Center and holds the J. Orin Edson Foundation Endowed Chair.

Gottardo plans to be at the vanguard of data-driven immunotherapy: “This will be a big theme in my lab in 2020, and we are working on this with several other labs and have begun cross-institute collaborations as well.”

New technologies to understand molecules and cells

Every area of science, however, will benefit in 2020 from high-powered technologies that are coming online in research institutes across the world, Hutch researchers said. They cited a range of new approaches for unlocking the secrets of cells’ activities that will become more commonly used in 2020. Among these is a cutting-edge microscopy approach called cryo-EM.

Short for “cryogenic electron microscopy,” cryo-EM enables researchers to learn the structures of molecules at a fine-grained scale never before possible, even for molecules and molecular complexes whose structures are unsolvable by all prior methods. It was such an advance that its developers won the 2017 Nobel Prize in chemistry. Understanding molecular structures is critical for understanding fundamental processes of life and for designing targeted therapies to inhibit molecules involved in disease.

Genome scientist Dr. Toshio Tsukiyama said 2020 will bring “an explosion of cryo-EM structure analyses” — including at the Hutch, which is gaining the ability to conduct cryo-EM in the new year, according to Senior Vice President and Basic Sciences Division Director Dr. Sue Biggins.

Cryo-EM “is a major step forward for biomedical science. In addition to providing fundamental mechanistic knowledge, it will allow inhibitors to be designed that could not be without the structural information that cryo-EM can provide,” said Biggins, who studies how cells sort their genetic material. “Having the ability to do this at the Hutch will be critical for advancing science, as well as treatments, from the Hutch.”

New insights from genomics

Tsukiyama and other Hutch experts expect 2020 will bring exciting advances in medicine and fundamental biology thanks to genomics.

It’s now easier, cheaper and faster than ever to read someone’s DNA code, learn the functions of its different parts and map out the complex wiring that controls all of it. (An illustrative example: One piece of that puzzle is genome sequencing, which is now roughly 100,000 times cheaper and 6.5 million times faster than it was when the Human Genome Project launched in 1991.) Consequently, scientists have now obtained the complete genome sequences of a huge list of living things whose diversity spans sharks, cockroaches, pear trees, athletes’ foot fungi and single-celled creatures living in deep-ocean volcanic vents.

Tsukiyama bets that scientists digging into those data sets will find some surprises in 2020.

“Because genome sequences of many organisms that are not traditionally used as models in basic and medical research have been determined, we will learn something astonishing about how life is controlled in some of these organisms,” said Tsukiyama, who is associate director of the Hutch’s Basic Sciences Division.

Genomics will become much more useful in individual human lives, said Fred Hutch’s Dr. Robert Bradley, who studies how cells process the instructions encoded in their DNA. He explained that genomics is now primarily a research tool, and the results of genomic experiments still come much too slowly for patients waiting for care. The coming year will bring a new focus on expediting that process, he predicted.

“I think that we’ll see an increased focus on using cancer genomics to inform precision medicine in real time, so that patient-care decisions can be made using the latest tools and analysis strategies,” Bradley said.

Gene therapy: easier to do, more applications

Beginning in 2017, a handful of therapies have been on the market that allow doctors to manipulate patients’ genetic codes to overcome disease.

Fred Hutch researchers see the momentum in gene therapy continuing to build in 2020.

“I predict that we will see more gene-editing technologies, and more gene-editing clinical protocols for both hematopoietic [blood-forming] stem cells and T cells,” said Dr. Hans-Peter Kiem, who directs the Hutch’s Stem Cell and Gene Therapy Program and holds the Stephanus Family Endowed Chair for Cell and Gene Therapy.

Among these new clinical protocols, hopes Dr. Justin Taylor, will be a first-in-human test of a therapy to genetically reprogram a patient’s B cells — a type of immune cell — to churn out specific disease-fighting antibodies.

“With all the interest in B-cell engineering, I expect the field to push towards the clinic in 2020,” Taylor said. “All the labs like ours that are working in this area are trying to make advances that would make this concept ready to be tested in humans.” 

And, trials of new gene therapy–based approaches are likely to get easier to do in 2020. That’s what Dr. Aude Chapuis said is the hopeful prediction of her research team, which is developing genetically engineered T-cell therapies for cancer.

“Genetic engineering technologies will continue to advance, and become more cost-effective and accessible to mainstream science, so that immune T cells can be efficiently engineered to target a wide variety of cancers at less cost,” Chapuis said. Her team also predicts that simplified regulatory requirements for launching new trials of these technologies will allow “faster translation of promising new treatments into clinical trials,” she said.

Accessibility of these technologies — now only performed in high-tech specialized labs — will also be an increasing research focus in 2020, Kiem said.

“I also predict that there will be increasing interest in 'in vivo' delivery platforms” — meaning ways to edit genes directly in a patient’s body, without needing a lab — “to make both gene therapy and editing more scalable,” he said.

“In 2020, new approaches to HIV prevention will be discovered, broadly neutralizing antibodies will be shown to be useful, and a new era of combination antibody therapy — where injections of two or more different broadly neutralizing antibodies are used to prevent infectious diseases — will begin,” Corey said, adding: “One needs to hit this virus at multiple points of attack.”   

Immunology expert Dr. Jennifer Lund looks forward to 2020 because her team will finally begin to analyze a “vast array of samples and data” from a study in Kenya of couples in which one person is HIV-positive and the other is HIV-negative. These data “could potentially allow for us to determine if there is something special about the immune system of chronically exposed individuals that helps to protect them from infection. This might help us identify targets for the design of future HIV vaccines or infection-prevention strategies,” Lund said.

Dr. Leslie Goo pointed toward another infectious disease we’ll make progress against in 2020: dengue fever, a mosquito-borne illness that kills 22,000 people annually, according to the Centers for Disease Control and Prevention. The dengue expert envisions discoveries in the coming year that will explain a perplexing aspect of dengue immunology: The immune response after a first dengue infection can make a second dengue infection worse. “Understanding the mechanisms behind this phenomenon will be important for guiding the design of safe and effective vaccines and drugs against dengue virus,” she said.

Public health will take more steps to control harms from vaping

Disease prevention, of course, goes far beyond the realms of vaccines and targeted infection-preventing drugs. Case in point: Public health efforts to minimize the use of tobacco and other nicotine-containing products. These killers are responsible for the deaths of more than 8 million people around the world each year from diseases like cancer and chronic obstructive pulmonary disease, according to the World Health Organization.

The newest iteration of this longstanding scourge is, of course, vaping and e-cigarettes. Fred Hutch lung cancer immunologist Dr. McGarry Houghton predicts that in 2020 more states will take action to control vaping, perhaps even enacting total bans. Such moves would follow on the heels of last week’s historic enactment of a national minimum age of 21 for tobacco (and vape) purchase to prevent teen addiction.

Last month, Houghton testified to the Washington state senate’s Health & Long-Term Care Committee about the evidence on vaping harms, as state lawmakers discuss what action to take, if any, on flavored vaping products — which research shows to have particular appeal to young users.

“All the things that the lungs have been asked to handle other than air have wound up being a problem over time,” he said during his testimony. “I think that’s an appropriate place to start when you’re considering the potential adverse health effects from vaping.”

— Fred Hutch News Service writers Jake Siegel, Sabrina Richards and Sabin Russell contributed reporting for this story.