Publisher Health

Around one in 500 men could be carrying an extra X or Y chromosome — most of them unaware — putting them at increased risk of diseases such as type 2 diabetes, atherosclerosis and thrombosis, say researchers at the universities of Cambridge and Exeter.
In a study published in Genetics in Medicine, researchers analysed genetic data collected on over 200,000 UK men aged 40-70 from UK Biobank, a biomedical database and research resource containing anonymised genetic, lifestyle and health information from half a million UK participants. They found 356 men who carried either an extra X chromosome or an extra Y chromosome.
Sex chromosomes determine our biological sex. Men typically have one X and one Y chromosome, while women have two Xs. However, some men also have an extra X or Y chromosome — XXY or XYY.
Without a genetic test, it may not be immediately obvious. Men with extra X chromosomes are sometimes identified during investigations of delayed puberty and infertility; however, most are unaware that they have this condition. Men with an extra Y chromosome tend to be taller as boys and adults, but otherwise they have no distinctive physical features.
In today’s study, the researchers identified 213 men with an extra X chromosome and 143 men with an extra Y chromosome. As the participants in UK Biobank tend to be ‘healthier’ than the general population, this suggests that around one in 500 men may carry an extra X or Y chromosome.
Only a small minority of these men had a diagnosis of sex chromosome abnormality on their medical records or by self-report: fewer than one in four (23%) men with XXY and only one of the 143 XYY men (0.7%) had a known diagnosis.

Inhaled aerosol vaccines provide far better protection and stronger immunity than nasal sprays, McMaster scientists who compared respiratory vaccine-delivery systems have confirmed.
While nasal sprays reach primarily the nose and throat, inhaled aerosols bypass the nasal passage and deliver vaccine droplets deep in the airway, where they can induce a broad protective immune response, the researchers report.
For the study, published online in the journal Frontiers in Immunology, the researchers used a tuberculosis vaccine to compare delivery methods by measuring the distribution of droplets, immune responses and potency in animals.When the vaccine was delivered directly into the lungs it stimulated stronger immune responses, providing much better protection from TB.
“Infections in the upper respiratory tract tend to be non-severe. In the context of infections caused by viruses like influenza or SARS-CoV-2, it tends to be when the virus gets deep into the lung that it makes you really sick,” explains Matthew Miller, a co-author of the study who holds the Canada Research Chair in Viral Pandemics at McMaster University.
“The immune response you generate when you deliver the vaccine deep into the lung is much stronger than when you only deposit that material in the nose and throat because of the anatomy and nature of the tissue and the immune cells that are available to respond are very different,” says Miller.
“This study for the first time provides strong preclinical evidence to support the development of inhaled aerosol delivery over nasal spray for human vaccination against respiratory infections including TB, COVID-19 and influenza,” says Zhou Xing, co-investigator of the study and a professor at the McMaster Immunology Research Centre and Department of Medicine.
More than 6.3 million have people died during the COVID-19 pandemic, and respiratory infections remain a significant cause of illness and death throughout the world, driving an urgent and renewed worldwide effort to develop vaccines that can be delivered directly to the mucous lining of the respiratory tract.
Scientists at McMaster, who have developed a unique inhaled form of COVID vaccine, believe this deep-delivery method offers the best defence against the current and future pandemics.
A Phase 1 clinical trial is currently under way to evaluate the inhaled aerosol vaccine in healthy adults who had previously received two or three doses of an injected COVID mRNA vaccine.
Nasal mist flu vaccines have been shown to be highly effective in children, but much less effective in adults, leaving injectable flu vaccines as the most popular choice for seasonal flu vaccinations.
Previous research by the McMaster team has shown that in addition to being needle-free and painless, an inhaled vaccine is so efficient at targeting the lungs and upper airways that it can achieve maximum protection with a much smaller dose than injected vaccines.
The research is part of Canada’s Global Nexus for Pandemics and Biological Threats at McMaster, which brings together an international network of researchers, government, industry, health care and other partners with the goal of finding solutions to the current pandemic, while preparing for future global health threats such as antimicrobial resistance.
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Materials provided by McMaster University. Original written by Michelle Donovan. Note: Content may be edited for style and length.

New estimates based on C.D.C. health surveys point to a stark generational shift in the growth of the transgender population of the United States.About 1.6 million people in the United States are transgender, and 43 percent of them are young adults or teenagers, according to a new report providing the most recent national estimates of this population.The analysis, relying on government health surveys conducted from 2017 to 2020, estimated that 1.4 percent of 13- to 17-year-olds and 1.3 percent of 18- to 24-year-olds were transgender, compared with about 0.5 percent of all adults.Those figures revealed a significant rise among younger people: The estimate of transgender people 13 to 25 nearly doubled since the researchers’ previous report, published in 2017, though the reports used different methods.The data point to a stark generational shift. Young people increasingly have the language and social acceptance to explore their gender identities, experts said, whereas older adults may feel more constrained. But the numbers, which vary widely from state to state, also raise questions about possible cultural drivers, such as the role of peer influence or the political climate of the community.“It’s developmentally appropriate for teenagers to explore all facets of their identity — that is what teenagers do,” said Dr. Angela Goepferd, medical director of the Gender Health Program at Children’s Hospital Minnesota, who was not involved in the new analysis. “And, generationally, gender has become a part of someone’s identity that is more socially acceptable to explore.”Dr. Goepferd, who is nonbinary, noted that many teenagers would not necessarily want or need medications or surgeries to transition to another gender, as was typical of older generations.The surveys, created by the Centers for Disease Control and Prevention, did not ask younger teenagers about nonbinary or other gender identities, which also have been rising in recent years. But nearly one-quarter of the adults in the surveys who said they were transgender identified as “gender nonconforming,” meaning they did not identify as a transgender man or woman.“We as a culture just need to lean into the fact that there is gender diversity among us,” Dr. Goepferd said. “And that it doesn’t mean that we need to treat it medically in all cases, but it does mean that we as a society need to make space for that.”Transgender Estimates by AgeTeenagers and adults under 25 make up an estimated 43 percent of the transgender population.

The tests screen for cancers that often go undetected, but they are expensive and some experts worry they could lead to unnecessary treatments without saving patients’ lives.Jim Ford considers himself a lucky man: An experimental blood test found his pancreatic cancer when it was at an early stage. It is the among the deadliest of all common cancers and is too often found too late.After scans, a biopsy and surgery, then chemotherapy and radiation, Mr. Ford, 77, who lives in Sacramento, has no detectable cancer.“As my doctor said, I hit the lottery,” he said.Tests like the one that diagnosed him have won praise from President Biden, who made them a priority of his Cancer Moonshot program. A bill in Congress with 254 cosponsors would authorize Medicaid and Medicare to pay for the tests as soon as the Food and Drug Administration approved them.But companies are not waiting for a nod from regulators. One, GRAIL, is selling its annual test, with a list price of $949, in advance of approval, and another company, Exact Sciences, expects to follow suit, using a provision known as laboratory developed tests.The tests, which look for minuscule shards of cancer DNA or proteins, are a new frontier in screening. Companies developing them say they can find dozens of cancers. While standard screening tests are commonly used to detect cancer of the breast, colon, cervix and prostate, but 73 percent of people who die of cancer had cancers that are not detected by standard tests.Supporters say the tests can slash cancer death rates by finding tumors when they are still small and curable. But a definitive study to determine whether the tests prevent cancer deaths would have to involve more than a million healthy adults randomly assigned to have an annual blood test for cancer or not. Results would take a decade or longer.“We’re at a point now where the blood tests are in their early days,” said Dr. Tomasz Beer, a cancer researcher at Oregon Health & Science University, who is directing a GRAIL-sponsored study of the test that found Mr. Ford’s cancer. “Some people in an informed manner can choose to be early adapters.”The companies would like to get the tests approved with studies less rigorous than the F.D.A. typically requires, and they stand to make huge profits if that happens.“GRAIL proposes to test every Medicare beneficiary every year, making it the screening test that could bankrupt Medicare,” said Dr. H. Gilbert Welch, a senior investigator in the Center for Surgery and Public Health at Brigham and Women’s Hospital.With 44 million Medicare beneficiaries and an annual test costing about $1,000 a year plus expensive scans and biopsies for those whose tests are positive, the price tag could be substantial.He and other critics warn that the risks of unleashing the tests are substantial. Paradoxical as it may sound, finding cancers earlier could mean just as many deaths, with the same timing as without early diagnosis. That is because — at least with current treatments — cancers destined to kill are not necessarily cured if found early.And there are other risks. For example, some will have a positive test, but doctors will be unable to locate the cancer. Others will be treated aggressively with surgery or chemotherapy for cancers that, if left alone, would not have grown and spread and may even have gone away.Dr. Beer acknowledges that a cancer blood test “doesn’t come without risks or costs, and it is not going to detect every cancer.”But, he said, “I think there’s promise for a real impact.”Others experts are worried.Dr. Barnett Kramer, a member of the Lisa Schwartz Foundation for Truth in Medicine and former director of the Division of Cancer Prevention at the National Cancer Institute, fears that the tests will come into widespread use without ever showing they are beneficial. Once that happens, he said, “it is difficult to unring the bell.”“I hope we are not halfway through a nightmare,” Dr. Kramer said.The Damocles SyndromeWhen Susan Iorio Bell, 73, a nurse who lives in Forty Fort, Pa., saw an ad on Facebook recruiting women her age for a study of a cancer blood test, she immediately signed up. It fit with her advocacy for preventive medicine and her belief in clinical trials.The study was of a test, now owned by Exact Sciences, that involved women who are patients with Geisinger, a large health care network. The test looks for proteins and DNA shed by tumors.Ms. Bell’s result was troubling: Alpha-fetoprotein turned up in her blood, which can signal liver or ovarian cancer.She was worried — her father had had colon cancer and her mother had breast cancer.Ms. Bell had seen what happened when patients get a dire prognosis. “All of a sudden, your life can be changed overnight,” she said.But a PET scan and abdominal M.R.I. failed to find a tumor. Is the test result a false positive, or does she have a tumor too small to be seen? For now, it is impossible to know. All Ms. Bell can do is have regular cancer screenings and monitoring of her liver function.“I just go day by day,” she said. “I am a faith-based person and believe God has a plan for me. Good or bad, it’s his will.”Some cancer experts say Ms. Bell’s experience exemplifies a concern with the blood tests. The situation may involve only a small percentage of people because most who are tested will be told their test did not find cancer. Among those whose tests detect cancer, scans or biopsies can often locate it.But Dr. Susan Domchek, a breast cancer researcher at the University of Pennsylvania, warned that when large numbers of people get tested, false positives become “a real problem,” adding, “we need to know what to do with those results and what they mean.”Dr. Daniel Hayes, a breast cancer researcher at the University of Michigan, refers to the situation as a Damocles syndrome: “You’ve got this thing hanging over your head, but you don’t know what to do about it.”How Good Are the Tests?So far, the Geisinger study is the only published one asking whether the blood tests find early, undetected cancers.In addition to Ms. Bell, the study involved 10,000 women aged 65 to 75 who had the blood test and were encouraged to also have routine cancer screening.The blood test found 26 patients who had cancers: two lymphomas, one thyroid cancer, one breast cancer, nine lung cancers, one kidney cancer, two colorectal cancers, one cancer of the appendix, two cancers of the uterus, six ovarian cancers and one unknown case in which there were cancer cells in the woman’s body but it was not clear where the cancer started.Seventeen of these women, or 65 percent, had early stage disease.Conventional screening found an additional 24 cancers that the blood tests missed.Dr. Bert Vogelstein, a cancer researcher at Johns Hopkins Medicine who helped to develop the test, said the study was not designed to show risks and benefits. That will require much larger and more detailed studies.GRAIL’s study, led by Dr. Beer, involved 6,629 participants. Its interim data, presented at a professional meeting last year, showed the test found cancer signals in 92 participants. After these subjects had additional tests like CT and PET scans and biopsies, the researchers concluded that 29 had cancer. Among those cancers, 23 were new cancers and nine were early stage. The rest were recurrences in people who had already had cancer.New Developments in Cancer ResearchCard 1 of 7Progress in the field.

Male sex hormones interfere with the body’s ability to fight bladder cancer, likely explaining why males experience higher cancer rates and more deadly disease, according to a new study co-led by a Cedars-Sinai Cancer investigator.
These findings, published in Science Immunology, could represent a significant step toward unraveling why disparities in cancer incidence, prognosis and treatment response exist between males and females. Males are more likely than females to develop most types of cancer. This is most evidently displayed in bladder cancer rates; studies show males are three to five times more likely than females to develop it.
“Historically, it was thought males may have higher cancer rates because they are more likely to engage in behaviors that predispose them to cancer, such as smoking,” said Xue Li, PhD, a senior and corresponding author of the study and research scientist at Cedars-Sinai. “We observed that biology of sex, not just behavior, is an important factor in cancer development.”
Androgens, sex hormones produced in higher amounts in males, promote the development of the reproductive system. Li and a team of investigators discovered that androgens interfere with the adaptive immune system, which comprises cells that remember how to respond to pathogens with which the body has previously come into contact. Androgens seem to block the activity of tumor-killing cells called CD8+ T cells, the investigators report.
Li and colleagues studied a mouse bladder cancer model in which more aggressive tumors arise in male mice, mimicking the incidence observed in humans. With this model, they experimented with removing various immune cells in mice of both sexes. When they removed CD8+ T cells, the male and female differences in cancer severity disappeared. This suggested that the way androgens interact with CD8+ T cells contributes to the sex differences in bladder cancer. Furthermore, the team found tumors grew more aggressively in mice with higher levels of androgens.
The most surprising finding, however, was observed when the team performed genetic sequencing of CD8+ T cells from the tumors, Li said. The CD8+ T cells in males showed more signs of exhaustion and dysfunction due to androgen activity. Androgen deprivation therapy, a common clinical treatment for prostate cancer, was effective in reducing bladder tumor size in male mice and improved the efficacy of immunotherapy.
The findings may explain in part why male and female patients respond differently to a type of cancer therapy called an immunotherapy, which helps the body’s CD8+ T cells attack cancer cells.
“T cells are like soldiers commissioned to kill tumor cells. However, they can become exhausted, so immunotherapy is used to rejuvenate them,” Li said. “Unfortunately, many cancer patients do not respond to immunotherapy. These findings suggest male patients may benefit more from immunotherapy when combined with androgen deprivation therapy.”
Li and colleagues plan to continue studying how and when androgen-inhibiting therapy may aid bladder cancer treatment. Similar to other cancers like breast cancer and prostate cancer that are affected by sex hormones, hormone therapy for bladder cancer may work best when given early in the course of the disease.
Funding: The study was funded by grants from the National Institutes of Health (R01 CA213290, R01 CA262069, R01 CA255334, R01 CA262338, R01 AI077283, R01 DK110477, U01 DK131377, R21 CA249701, and K08AI139375), a Young Investigator Award from the Prostate Cancer Foundation, the Damon Runyon Clinical Investigator Award, the Doctoral Foreign Study Award from the Canadian Institutes of Health Research (201810DFS-422133-63414), a Graduate Fellowship from the Medical University of South Carolina Hollings Cancer Center, and the Ohio State University Comprehensive Cancer Center Tumor Immunology T32 Training Program (2T32CA09223-16A1).

A new study highlights how closely connected politics and health outcomes have grown over time. Investigators from Brigham and Women’s Hospital examined mortality rates and federal and state election data for all counties in the U.S. from 2001 to 2019. The team found what they call a “mortality gap” — a widening difference between age-adjusted death rates in counties that had voted for a Democrat or a Republican in previous presidential and governor elections. The team found that mortality rates decreased by 22 percent in Democratic counties but by only 11 percent in Republican counties. The mortality gap rose across top disease areas, including heart disease and cancer, and the mortality gap between white residents in Democratic versus Republican counties increased nearly fourfold during the study period. Results are published in the British Medical Journal.
“In an ideal world, politics and health would be independent of each other and it wouldn’t matter whether one lives in an area that voted for one party or another,” said corresponding author Haider Warraich, MD, of the Division of Cardiovascular Medicine at the Brigham. “But that is no longer the case. From our data, we can see that the risk of premature death is higher for people living in a county that voted Republican.”
Warraich and colleagues used data from the Wide-ranging OnLine Data for Epidemiologic Research (CDC WONDER) database and the MIT (Massachusetts Institute of Technology) Election Data and Science Laboratory. They classified counties as Democratic or Republican based on the way the county had voted in the previous presidential election and adjusted for age when calculating mortality rates.
Overall, the team found that mortality rates in Democratic counties dropped from 850 deaths per 100,000 people to 664 (22 percent), but in Republican counties, mortality rates declined from 867 to 771 (11 percent). When the team analyzed by race, they found that there was little gap between the improvements in mortality rates that Black and Hispanic Americans experienced in Democratic and Republican counties. But among white Americans, the gap between people living in Democratic versus Republican counties was substantial.
The mortality gap remained consistent when the researchers looked only at counties that had voted Republican or Democratic in every presidential election year studied and when they looked at gubernatorial elections. Democratic counties experienced greater reductions in mortality rates across most common causes of death, including heart disease, cancer, chronic lower respiratory tract diseases, diabetes, influenza and pneumonia, and kidney disease.
The authors note that the widening gap in death rates may reflect the influence of politics on health policies. One of the inflection points detected in the study corresponds to the Affordable Care Act (ACA), which was passed in 2010. More Democratic states than Republican states adopted Medicaid expansion under the ACA, which expanded health insurance coverage to people on a low income.
The study detects an association between political environment and mortality but does not definitively determine the direction of the association or the specific factors that may explain the link between the two. The authors did not study the effect of flipping political environments — that is, counties that switched from voting Democratic or Republican to voting for the other party — on health outcomes, which could be an area of future study. The study period ended in 2019, before the start of the COVID-19 pandemic, which may have had an even more profound impact on the mortality gap.
“Our study suggests that the mortality gap is a modern phenomenon, not an inevitability,” said Warraich. “At the start of our study, we saw little difference in mortality rates in Democratic and Republican counties. We hope that our findings will open people’s eyes and show the real effect that politics and health policy can have on people’s lives.”
Disclosures: Warraich is an advisor for Embrace Prevention Care; co-author Rishi Wadhera receives research support from the National Heart, Lung, and Blood Institute (grant K23HL148525-1); co-author Karen E. Joynt Maddox previously did contract work for the U.S. Department of Health and Human Services.
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A new molecule synthesized by a University of Texas at Dallas researcher kills a broad spectrum of hard-to-treat cancers, including triple-negative breast cancer, by exploiting a weakness in cells not previously targeted by other drugs.
A study describing the research — which was carried out in isolated cells, in human cancer tissue and in human cancers grown in mice — was published online June 2 in the journal Nature Cancer.
Dr. Jung-Mo Ahn, a co-corresponding author of the study and a UT Dallas associate professor of chemistry and biochemistry in the School of Natural Sciences and Mathematics, has been passionate about his work designing small molecules that target protein-protein interactions in cells for over a decade. Using an approach called structure-based rational drug design, he previously developed potential therapeutic candidate compounds for treatment-resistant breast cancer and for prostate cancer.
In the current work, Ahn and his colleagues tested a novel compound he synthesized called ERX-41 for its effects against breast cancer cells, both those that contain estrogen receptors (ERs) and those that do not. While there are effective treatments available for patients with ER-positive breast cancer, there are few treatment options for patients with triple-negative breast cancer (TNBC), which lacks receptors for estrogen, progesterone and human epidermal growth factor 2. TNBC generally affects women under 40 and has poorer outcomes than other types of breast cancer.
“The ERX-41 compound did not kill healthy cells, but it wiped out tumor cells regardless of whether the cancer cells had estrogen receptors,” Ahn said. “In fact, it killed the triple-negative breast cancer cells better than it killed the ER-positive cells.
“This was puzzling to us at the time. We knew it must be targeting something other than estrogen receptors in the TNBC cells, but we didn’t know what that was.”
To investigate the ERX-41 molecule, Ahn worked with collaborators, including co-corresponding authors Dr. Ganesh Raj, professor of urology and pharmacology at the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern Medical Center, as well as Dr. Ratna Vadlamudi, professor of obstetrics and gynecology at UT Health San Antonio. Dr. Tae-Kyung Lee, a former UTD research scientist in Ahn’s Bio-Organic/Medicinal Chemistry Lab, was involved in synthesizing the compound.

From the moment we are born, and even before that, we interact with the world through movement. We move our lips to smile or to talk. We extend our hand to touch. We move our eyes to see. We wiggle, we walk, we gesture, we dance. How does our brain remember this wide range of motions? How does it learn new ones? How does it make the calculations necessary for us to grab a glass of water, without dropping it, squashing it, or missing it?
Technion Professor Jackie Schiller from the Ruth and Bruce Rappaport Faculty of Medicine and her team examined the brain at a single-neuron level to shed light on this mystery. They found that computation happens not just in the interaction between neurons (nerve cells ), but within each individual neuron. Each of these cells, it turns out, is not a simple switch, but a complicated calculating machine. This discovery, published recently in the Science magazine, promises changes not only to our understanding of how the brain works, but better understanding of conditions ranging from Parkinson’s disease to autism. And if that weren’t enough, these same findings are expected to advance machine learning, offering inspiration for new architectures.
Movement is controlled by the primary motor cortex of the brain. In this area, researchers are able to pinpoint exactly which neuron(s) fire at any given moment to produce the movement we see. Prof. Schiller’s team was the first to get even closer, examining the activity not of the whole neuron as a single unit, but of its parts.
Every neuron has branched extensions called dendrites. These dendrites are in close contact with the terminals (called axons) of other nerve cells, allowing the communication between them. A signal travels from the dendrites to the cell’s body, and then transferred onwards through the axon. The number and structure of dendrites varies greatly between nerve cells, like the crown of one tree differs from the crown of another.
The particular neurons Prof. Schiller’s team focused on were the largest pyramidal neurons of the cortex. These cells, known to be heavily involved in movement, have a large dendritic tree, with many branches, sub-branches, and sub-sub-branches. What the team discovered is that these branches do not merely pass information onwards. Each sub-sub-branch performs a calculation on the information it receives and passes the result to the bigger sub-branch. The sub-branch than performs a calculation on the information received from all its subsidiaries and passes that on. Moreover, multiple dendritic branchlets can interact with one another to amplify their combined computational product. The result is a complex calculation performed within each individual neuron. For the first time, Prof. Schiller’s team showed that the neuron is compartmentalised, and that its branches perform calculations independently.
“We used to think of each neuron as a sort of whistle, which either toots, or doesn’t,” Prof. Schiller explains. “Instead, we are looking at a piano. Its keys can be struck simultaneously, or in sequence, producing an infinity of different tunes.” This complex symphony playing in our brains is what enables us to learn and perform an infinity of different, complex and precise movements.
Multiple neurodegenerative and neurodevelopmental disorders are likely to be linked to alterations in the neuron’s ability to process data. In Parkinson’s disease, it has been observed that the dendritic tree undergoes anatomical and physiological changes. In light of the new discoveries by the Technion team, we understand that as a result of these changes, the neuron’s ability to perform parallel computation is reduced. In autism, it looks possible that the excitability of the dendritic branches is altered, resulting in the numerous effects associated with the condition. The novel understanding of how neurons work opens new research pathways with regards to these and other disorders, with the hope of their alleviation.
These same findings can also serve as an inspiration for the machine learning community. Deep neural networks, as their name suggests, attempt to create software that learns and functions somewhat similarly to a human brain. Although their advances constantly make the news, these networks are primitive compared to a living brain. A better understanding of how our brain actually works can help in designing more complex neural networks, enabling them to perform more complex tasks.
This study was led by two of Prof. Schiller’s M.D.-Ph.D. candidate students Yara Otor and Shay Achvat, who contributed equally to the research. The team also included postdoctoral fellow Nate Cermak (now a neuroengineer) and Ph.D. student Hadas Benisty, as well as three collaborators: Professors Omri Barak, Yitzhak Schiller, and Alon Poleg-Polsky.
The study was partially supported by the Israeli Science Foundation, Prince funds, the Rappaport Foundation, and the Zuckerman Postdoctoral Fellowship.

A protein that the body naturally produces could become an important new immunotherapy drug in the cache of cancer-fighting tools available to oncologists. UC Davis cancer researchers for both companion dogs and humans joined scientists from other institutions to study a new approach that triggers the body’s defense mechanisms, its T-cells and natural killer (NK) cells, to respond and destroy cancer.
Surgical oncologist Robert J. Canter with UC Davis Comprehensive Cancer Center and canine oncologist Robert B. Rebhun with the UC Davis School of Veterinary Medicine are corresponding authors for a study just published in the Journal for ImmunoTherapy of Cancer.
In the first-of-its-kind Phase 1 clinical trial, 21 pet dogs of various breeds that had metastatic lung disease resulting from osteosarcoma or melanoma were treated with protein interleukin-15 (IL-15). Although previously recognized for immunotherapy properties, IL-15 has undergone few human clinical trials because of toxicity risks associated with concentrated doses.
“No one previously had administered IL-15 as an inhaled treatment in dogs to deliver it directly to the site of the cancer. We came up with that idea as a means of reducing exposure to the rest of the body, in order to improve the benefit-risk ratio, to improve the immune stimulating effects, and to reduce toxicity,” Canter explained. “In this study, we used interleukin-15 to reinvigorate the immune system to make it recognize the cancer cells that had evaded the immune system and eliminate them.”
The research shows that amplified concentrations of IL-15 can stimulate immune system defenses against some types of cancers in dogs. IL-15 is one of several types of cytokines — substances that have signaling and regulating functions in immune system activity.
“As part of our comparative oncology research, we are strong advocates of clinical trials in companion dogs, especially for immunotherapy, as a way to speed bench-to-bedside translation,” said Canter, who is chief of the UC Davis Division of Surgical Oncology and co-director of the comparative oncology training program at UC Davis. “The cancers that afflict dogs, including sarcomas, brain tumors, lymphoma and melanoma, are incredibly similar to cancers that humans develop.”
UC Davis received a $2 million National Cancer Institute grant to fund the comparative oncology training program to support the next generation of oncology researchers collaborating on curing cancer in both humans and dogs. For instance, osteosarcoma and melanoma that develop elsewhere in the body commonly spread to the lung, in dogs as well as humans.