Experimental Cancer Vaccine Shows Promise in Animal Studies

An experimental therapeutic cancer vaccine induced two distinct and desirable immune system responses that led to significant tumor regression in mice, report investigators from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.  

The researchers found that intravenous (IV) administration of the vaccine boosted the number of cytotoxic T cells capable of infiltrating and attacking tumor cells and engaged the innate immune system by inducing type I interferon. The innate immune response modified the tumor microenvironment, counteracting suppressive forces that otherwise would tamp down T-cell action. Modification of the tumor microenvironment was not seen in mice that received the vaccine via needle injection into the skin (subcutaneous administration).

Dubbed “vax-innate” by the scientific team, the approach achieves an important goal in the quest for more effective immunotherapeutic vaccines for cancer. The study demonstrates that IV vaccine delivery enables and enhances T-cell immunity by overcoming tumor-induced immunosuppressive activity. The researchers say the candidate vaccine might also be given intravenously to people who have already received tumor-specific T cells as a therapy. It also could improve tumor control by increasing the number of T cells and altering the tumor microenvironment to make them function better, the researchers note. 

Roche launches a new system for timely cancer diagnostics targeted patient care

Roche (SIX: RO, ROG; OTCQX: RHHBY) announced the launch of the BenchMark ULTRA PLUS system, its newest advanced tissue staining platform. The system enables quick and accurate test results so clinicians can make timely decisions regarding a patient’s care journey.

“Over one million cases of cancer are diagnosed in Africa each year². With many African communities living in rural areas or far from healthcare centres, waiting for a diagnosis is often one of the most stressful times. The BenchMark ULTRA PLUS enables pathologists to provide quick and accurate results that help inform patient treatment options, timeously.” says Alan Yates Ad-Interim General Manager South Africa & SADC markets, Roche Diagnostics.

Cancer and other abnormal cells can be characterised by biochemical markers from within the cells. By applying chemical solutions to tissue on glass slides with the BenchMark ULTRA PLUS, a healthcare professional can identify these markers to determine the presence or absence of key drivers that feed the unhealthy cells and, in many cases, the type of therapy that could be used to combat them³.

The new BenchMark ULTRA PLUS system continues the evolution of the BenchMark series, which revolutionised cancer diagnostics by fully automating processes that used to be performed manually, one slide at a time.

Lab personnel will be able to manage their activities more efficiently as a result of simplified software and streamlined productivity and quality control. These enhancements can help support the quicker delivery of test results for patients who are waiting for a diagnosis.

The new system has several innovations such as new intuitive software, remote monitoring features, an integrated touchscreen for a more optimised user experience, and a more environmentally sustainable waste system and product packaging^1&4.

The BenchMark ULTRA PLUS system will be available in South Africa, Zimbabwe, Zambia, Malawi, Lesotho, Namibia and Mauritius in 2023.

Tobacco smoking rates are decreasing in people with major depression and substance use disorder

Significant reductions in cigarette use were found among U.S. adults with major depression, substance use disorder, or both from 2006 to 2019, according to a new analysis of nationally representative survey data published today in JAMA. 

Smoking is a modifiable risk factor for cardiovascular disease and 73% of African American adults who smoke want to quit,

The study was conducted by researchers at the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health, and the Substance Abuse and Mental Health Services Administration (SAMHSA).

These findings suggest that groups at higher risk of cigarette smoking can be reached by, and may have benefitted from, tobacco use prevention and cessation efforts that have led to significant declines in tobacco use in the general population. At the same time, the findings highlight remaining disparities, documenting higher smoking rates in people with psychiatric disorders than in those without.

“This study shows us that, at a population-level, reductions in tobacco use are achievable for people with psychiatric conditions, and smoking cessation should be prioritized along with treatments for substance use, depression, and other mental health disorders for people who experience them,” said Nora Volkow, M.D., director of NIDA and co-author of the study. “Therapies to help people stop smoking are safe, effective, and may even enhance the long-term success of concurrent treatments for more severe mental health symptoms in individuals with psychiatric disorders by lowering stress, anxiety, depression, and by improving overall mood and quality of life.”

Cigarette smoking, the leading preventable cause of disease, disability and death in the U.S., has been declining. Experts attribute this in part to increases in available treatments, insurance coverage of these treatments, cigarette prices, smoke-free and tobacco-free policies, mass media and educational campaigns and other evidence-based strategies to help people avoid or quit using cigarettes that have been implemented in recent decades.

Quitting cigarette smoking and tobacco use reduces the risk of cancer, heart disease, stroke and lung diseases. Studies have also found that smoking cessation in people with psychiatric disorders can help decrease anxiety, depression and stress; lower likelihood of a new-onset substance use disorder; and improve quality of life.

Past studies have documented that smoking rates remained essentially unchanged in people with substance use disorders, major depression or other psychiatric disorders. Now, analyzing data from more than 558,000 individuals aged 18 and older who participated in the 2006 to 2019 National Surveys on Drug Use and Health (NSDUH), researchers found that while people with major depression, substance use disorder or both were more likely to smoke cigarettes than people without these disorders; improvements in smoking cessation were seen among those with these psychiatric disorders during the 14-year period. The NSDUH, conducted annually by SAMHSA, provides nationally representative data on cigarette smoking, tobacco use, major depressive episode and substance (alcohol or drug) use disorders among the US civilian, non-institutionalized adult population. Among the population studied here, roughly 53% were women, 41% were aged 18 to 25 and 62% were non-Hispanic white.

After controlling for factors such as age, sex, race/ethnicity, education and family income, the researchers found that past-month smoking rates declined by 13.1% from 2006 to 2019 among adults with a past-year major depressive episode and by 8.2% from 2006 to 2019 among adults without. The difference in past-month cigarette smoking among those with versus without past-year major depressive episode significantly narrowed from 11.5% in 2006 to 6.6% in 2019.

Similarly, past-month cigarette smoking declined by 10.9% from 2006 to 2019 among adults with past-year substance use disorder and by 7.8% among adults without. For people with co-occurring substance use disorder and major depression, past-month smoking rates decreased by 13.7% during this 14-year period and by 7.6% among adults without these disorders.

“These declines tell a public health success story,” said Wilson Compton, M.D., NIDA’s Deputy Director and the senior author of the study. “However, there’s still a lot of work to be done to ensure tobacco use in patients with substance use disorder, depression, or other psychiatric conditions continue to decrease. It is crucial that healthcare providers treat all the health issues that a patient experiences, not just their depression or drug use disorder at a given point in time. To do this, smoking cessation therapies need to be integrated into existing behavioral health treatments. The result will be longer and healthier lives for all people.”

During 2006 to 2019, among adults with past-year major depressive episodes or substance use disorder, past-month cigarette smoking declined significantly across every examined age, sex, and racial and ethnic subgroup, except that among non-Hispanic American Indian or Alaska Native adults smoking rates did not decline. Given that American Indian and Alaska Native communities face the highest smoking and lowest quitting rates among racial and ethnic subgroups in the United States, this highlights the need to channel additional prevention and treatment efforts into these communities.

In future work, the researchers note the need to include data on certain populations at high risk of psychiatric disorders and cigarette smoking, such as institutionalized individuals or those experiencing homelessness without living in a shelter. More work is also needed to continue to monitor national trends in differences in tobacco use and nicotine vaping among adults with or without psychiatric conditions – including substance use disorder – during the COVID-19 pandemic.

NIH launches program to offer molecular characterization of childhood cancers

In support of President Biden’s Cancer Moonshot℠ goal of fostering data sharing in cancer research, the National Cancer Institute, part of the National Institutes of Health, has launched the Molecular Characterization Initiative for pediatric tumors.

The program offers tumor molecular characterization, also called biomarker testing, to children, adolescents, and young adults with newly diagnosed central nervous system tumors who are being treated at hospitals that are affiliated with the Children’s Oncology Group (COG)(link is external), an NCI-supported clinical trials group that includes more than 200 hospitals and institutions that treat most children diagnosed with cancer in the United States.

The Molecular Characterization Initiative is offered through NCI’s Childhood Cancer Data Initiative, which was launched in 2019 to promote data sharing and collection of new data among researchers who study childhood cancers.

Children, adolescents, and young adults diagnosed with a central nervous system cancer across the United States will be eligible to receive molecular characterization of their tumors free of charge through this voluntary program. DNA and RNA from tumor and blood samples will be analyzed to help make an accurate diagnosis and to understand what is causing or driving the cancer. The Molecular Characterization Initiative will expand later in 2022 to include soft tissue sarcomas and other rare tumors.

“The ultimate dream has really been for every child with cancer to have a state-of-the-art diagnosis and the safest and most effective therapy,” said Brigitte C. Widemann, M.D., special advisor to the NCI director for childhood cancer. “The Molecular Characterization Initiative is a transformative collaboration that will entail participation of the entire community.”

Having a precise diagnosis based on the molecular characteristics of a patient’s tumor can help doctors choose the most effective and potentially least toxic treatment for each child. Data on the molecular changes seen across childhood cancers can also help researchers better understand the molecular causes of childhood cancers and accelerate the development of new, more effective, and potentially less toxic treatments, especially for rare childhood cancers for which treatment options are limited. 

“The game changer for patients is that we’re going to understand the patient’s disease precisely and comprehensively in a way that we’ve done piecemeal so far,” said Douglas S. Hawkins, M.D., group chair of COG.

Previously, comprehensive tumor molecular characterization was available to children enrolling in some clinical trials or to those being treated at larger institutions with internal resources to offer such state-of-the-art diagnostics. Data on tumor biomarkers were stored exclusively at the hospital or institution where a child was treated, with limited sharing of data among institutions. The new program will make tumor molecular characterization broadly available for children throughout the country. Moreover, the data collected will be available in a central location so that childhood cancer researchers can learn from the data and use it to inform future studies.

“We can help make molecular characterization available throughout the country so that it will be a standard of care that every child can get,” said Maryam Fouladi, M.D., COG’s central nervous system tumor disease committee leader. “An accurate molecular diagnosis can inform optimal treatment for every child.”

For example, Dr. Fouladi explained, some childhood cancers, such as gliomas, can be misdiagnosed. “We can apply molecular diagnostics to a child diagnosed with a high-grade glioma and find out that it is actually a low-grade glioma or an entirely different tumor, which may need very different treatments and have a very different outcome,” she said. “Molecular diagnostics can really contribute to getting the correct diagnosis, offering the optimal treatment and, ultimately, improving the patient’s outcome.”

In addition to providing detailed information about a cancer to use in making an accurate diagnosis, the data can also be used to determine whether a child is eligible for a clinical trial. Molecular characterization can reveal, for example, whether a child has a specific cancer subtype that is eligible for a clinical trial evaluating a new treatment explicitly designed for that subtype.

Enrollment in the Molecular Characterization Initiative is initially offered through participation in Project:EveryChild(link is external), a childhood cancer registry maintained by COG (APEC14B1). Initial participants will include newly diagnosed children, adolescents, and young adults ages 25 years and younger at the time of diagnosis. Young adults over the age of 25 who are being screened for eligibility into a COG clinical trial may also be included.

Tumor and blood samples from participants will be sent to an accredited lab for analysis, and the results will be available to patients and their families within 21 days. The molecular data will also be aggregated into a database available to researchers for future studies, such as those exploring why some tumors become resistant to therapies they initially responded to or what factors increase the risk of treatment-related side effects. Personal information that could be used to identify a participant will be removed before data are put into the database.

Dr. Widemann said the Molecular Characterization Initiative is a program the childhood cancer community can easily get behind. “To be able to apply the best tools to make the most accurate diagnosis so that the most effective treatment can be prescribed, that’s a goal that I think physicians and families can all align around,” she said.

A high-fiber diet may improve the response of melanoma patients to immunotherapy

A diet rich in fiber may help some people being treated for melanoma respond to immunotherapy treatment by influencing the gut microbiome, according to a new study led by researchers at the Center for Cancer Research at the National Cancer Institute (NCI), part of the National Institutes of Health, and the University of Texas MD Anderson Cancer Center. Results from the study, which analyzed both people with melanoma and mouse models of the disease, appear in Science.

Among patients with advanced melanoma who underwent immunotherapy with immune checkpoint blockers, those who consumed at least 20 grams a day of dietary fiber survived the longest without their disease progressing. In contrast, use of probiotic supplements appeared to lessen somewhat the effectiveness of immune checkpoint blocker regimens. Probiotics are live microorganisms typically consumed as a supplement to improve gut health.

“The data suggest that one can target the composition of the gut microbiota and affect the ability of the patient to respond to immunotherapy,” said Giorgio Trinchieri, M.D., chief of the Laboratory of Integrative Cancer Immunology in NCI’s Center for Cancer Research, one of the study’s coleaders. “Consuming a diet rich in fiber, like fruits, vegetables, and legumes, could improve your ability to respond to immunotherapy.”

Immunotherapy with immune checkpoint blockers helps restore the immune system’s natural ability to recognize and kill tumor cells. These drugs have been transformative in melanoma, improving how long some people with advanced disease live, sometimes by years. However, for many patients, immune checkpoint blockers fail to stop their tumors from growing. Several studies have suggested that the composition of the bacteria in the gut may influence the response to immunotherapy.

“The question is, can we change the composition of the type of bacteria in the gut and improve the ability of the patient to respond?” Dr. Trinchieri said.

In a previous study, Dr. Trinchieri and a different group of collaborators showed that some people with melanoma who initially did not respond to treatment with an immune checkpoint blocker did respond after receiving a fecal transplant from a patient who had responded to the drug. The fecal transplant, they concluded, had introduced different gut bacteria that helped make it easier for immune cells to invade and kill their tumors.

“Dietary fiber intake and use of probiotic supplements have also been shown to affect the composition of gut bacteria. More cancer patients are taking probiotic supplements in an effort to improve their gut health, but little is known about how probiotics—which basically change the ecology of the gut bacteria—impact immunotherapy response,” he said.

The connection between fiber intake and immunotherapy response has also been unclear. However, a recent study led by Romina Goldszmid, Ph.D., also of NCI’s Center for Cancer Research, showed that mice fed a diet rich in pectin, which is a fiber abundant in apples, were able to stave off tumor growth by activating immune cells and reprogramming the tumor microenvironment.

In the new study, Dr. Trinchieri and study co-leads Carrie R. Daniel, Ph.D., M.P.H., and Jennifer A. Wargo, M.D., of the University of Texas MD Anderson Cancer Center, and their collaborators looked at the composition of fecal microorganisms (the gut microbiota), dietary habits, and probiotic supplement use among patients who were being treated for advanced melanoma with immune checkpoint blockers.

Among the 128 patients whose dietary fiber intake was known, those who reported consuming at least 20 grams of dietary fiber per day (an amount the researchers designated as “sufficient” for the purposes of this study) lived longer without their cancer progressing than those who consumed less dietary fiber. Every 5-gram increase in daily dietary fiber intake corresponded to a 30% lower risk of progression of the disease.

The researchers also looked at the impact of dietary fiber on the response to treatment with anti-PD-1 drugs, a category of immune checkpoint blockers, in mouse models of melanoma. To mimic the different diets in the melanoma patients, they fed mice either a fiber-rich or a low-fiber diet, injected the mice with melanoma cells, and then treated the mice with anti-PD-1 therapy. Mice given the fiber-rich diet had delayed tumor growth after anti-PD-1 treatment, compared with mice given the low-fiber diet.

The researchers then repeated the experiments in germ-free mice—that is, mice that have no bacteria in their guts.

“In germ-free mice, the diet made no difference in the immunotherapy response,” Dr. Trinchieri said. “That suggests that the diet is affecting the response to immune checkpoint therapy by changing the composition of the gut microbiota.”

Dr. Trinchieri noted that one possible mechanism through which dietary fiber exerts its beneficial effect is by increasing the types of bacteria in the gut, such as Ruminococcaceae, that produce high levels of certain short-chain fatty acids that have an antitumor effect.

“We did see an increase in one of these short-chain fatty acids, propionate, in mice that were fed a high-fiber diet,” Dr. Trinchieri said. “Moreover, patients whose cancer responded to immunotherapy had a greater abundance of Ruminococcaceae bacteria in their gut microbiota compared with those who did not respond to therapy.”

The researchers also looked at the impact of probiotics on gut bacteria in the mouse model of melanoma. Mice fed probiotics had a reduced response to treatment with anti-PD-L1 drugs and developed larger tumors than control mice. Further analysis showed that mice fed probiotics had lower levels of tumor-killing immune cells, suggesting a weakened immune response.

In the human study, nearly one-third of the patients reported they had taken a probiotic supplement within the past month. Although the researchers noted that the small sample size and variety of probiotics used by the patients made it difficult to draw definitive conclusions about the association between probiotic use and response to immune checkpoint blockers, they did observe that patients who consumed the highest levels of dietary fiber with no probiotic use survived the longest.

“The impact of dietary fiber and probiotics on the gut microbiota is only part of the bigger picture,” Dr. Trinchieri cautioned. “Many factors can affect the ability of a patient with melanoma to respond to immunotherapy. However, from these data, the microbiota seems to be one of the dominant factors. The data also suggest that it’s probably better for people with cancer receiving immunotherapy not to use commercially available probiotics.”

WHO and St. Jude to dramatically increase global access to childhood cancer medicines

The World Health Organization and St. Jude Children’s Research Hospital today announced plans to establish a platform that will dramatically increase access to childhood cancer medicines around the world.

The Global Platform for Access to Childhood Cancer Medicines, the first of its kind, will provide an uninterrupted supply of quality-assured childhood cancer medicines to low- and middle-income countries. St. Jude is making a six-year, US$ 200 million investment to launch the platform, which will provide medicines at no cost to countries participating in the pilot phase. This is the largest financial commitment for a global effort in childhood cancer medicines to date. 

“Close to nine in ten children with cancer live in low- and middle-income countries,” said Dr Tedros Adhanom Ghebreyesus, WHO Director-General. “Survival in these countries is less than 30%, compared with 80% in high-income countries. This new platform, which builds on the success of the Global Initiative for Childhood Cancer launched with St. Jude in 2018, will help redress this unacceptable imbalance and give hope to many thousands of parents faced with the devastating reality of a child with cancer.” 

Affordable, good quality and uninterrupted cancer medicines for children

Each year, an estimated 400 000 children worldwide develop cancer. The majority of children living in low- and middle-income countries are unable to consistently obtain or afford cancer medicines. As a result, nearly 100 000 children die each year. 

The new platform aims to provide safe and effective cancer medicines to approximately 120 000 children between 2022 and 2027, with the expectation to scale up in future years. This platform will provide end-to-end support  ̶  consolidating global demand to shape the market; assisting countries with the selection of medicines; developing treatment standards; and building information systems to track that effective care is being provided and to drive innovation. 

“St. Jude was founded on the mission to advance research and treatment of childhood cancer and other catastrophic pediatric diseases. Nearly 60 years later, we stand with the World Health Organization, partner organizations and our Global Alliance collaborators to expand that promise for children worldwide,” said James R. Downing, M.D., president and CEO of St. Jude. “With this platform, we are building the infrastructure to ensure that children everywhere have access to safe cancer medicines.”

This innovative approach will open a new chapter in access to cancer care by addressing medicine availability in low- and middle-income countries that is often complicated by higher prices, interruptions in supply and out-of-pocket expenditures that result in financial hardship.

According to a WHO Noncommunicable Disease Country Capacity survey published in 2020, only 29% of low-income countries report that cancer medicines are generally available to their populations compared to 96% of high-income countries. By consolidating the needs of children with cancer globally, the new platform will curtail the purchasing of sub-standard and falsified medicines that results from unauthorized purchases and the limited capacity of national regulatory authorities.

“Unless we address the shortage and poor quality of cancer medicines in many parts of the world, there are very few options to cure these children,” said Carlos Rodriguez-Galindo, M.D., executive vice president and chair of the St. Jude Department of Global Pediatric Medicine and director of St. Jude Global. “Health-care providers must have access to a reliable source of cancer medicines that constitute the current standard of care. We at St. Jude, with our co-founding partners at WHO and many vital partners around the world, can help achieve that.” 

“WHO, St Jude and partners will spare no efforts to get children’s access to cancer medicines on track,” added Dr Bente Mikkelsen, Director of the Department of Noncommunicable Diseases at WHO. “WHO is on the ground, working with governments to deliver support and services to ensure that all children have access to the best cancer treatment possible.”

Pilot phase in 12 countries

During an initial two-year pilot phase, medicines will be purchased and distributed to 12 countries through a process involving governments, cancer centers and nongovernmental organizations already active in providing cancer care. Discussions are already ongoing with governments to determine the countries which will participate in this pilot phase. By the end of 2027, it is expected that 50 countries will receive childhood cancer medicines through the platform.  

Kathy Pritchard-Jones, president of the International Society of Paediatric Oncology, said; “We look forward to working with St. Jude and WHO on this journey to ensure all children, everywhere, have access to quality cancer medicines. The platform is bringing forth a dream of our more than 2600 global members.” 

João Bragança, president of Childhood Cancer International, added: “Cancer should not be a death sentence, no matter where a child lives. By developing this platform, St. Jude is helping families get access to lifesaving medicines for their children. Working together, we can change the outcome for cancer-afflicted children around the world.” 

Quitting smoking after lung cancer diagnosis may extend life without cancer recurrence

A prospective cohort study found that quitting smoking after being diagnosed with early-stage non-small cell lung cancer may slow disease progression and decrease mortality.

Given that about half of all smokers continue to smoke after a lung cancer diagnosis, these findings present an opportunity to improve overall and progression-free survival in this type of cancer.

The study is published in Annals of Internal Medicine.

More than 80% of patients with non-small cell lung cancer have a history of smoking, and about half are current smokers at the time of diagnosis.

There is limited evidence that smoking cessation may improve survival, so many patients may feel it is too late to quit once they’ve been diagnosed with lung cancer.

Researchers from the International Agency for Research on Cancer, the specialised cancer agency of the World Health Organization, in collaboration with the N.N. Blokhin National Medical Research Centre of Oncology in Russia, recruited 517 adults who currently smoked when diagnosed with early-stage non-small cell lung cancer from 2 sites in Moscow, Russia to determine whether quitting smoking after diagnosis affects the risk for disease progression and mortality.

The participants were interviewed at the start of the study to ascertain medical and lifestyle history, including tumour characteristics, and the amount of lifetime smoking, and then followed each year for an average of 7 years to record any changes in their smoking behaviour, treatments, and disease status.

Of 517 patients who were smoking when diagnosed with lung cancer, less than half quit (44.5%), and very few relapsed.

The patients who quit smoking were more likely to live longer overall (6.6 years vs. 4.8. years), live longer without lung cancer (5.7 vs. 3.9 years) and have a longer time to death from lung cancer (7.9 vs. 6 years).

According to the authors, these results show that even after being diagnosed with lung cancer, there is still significant benefit to quitting smoking.

Physicians should make their lung cancer patients aware that quitting smoking can extend life overall and extend life without cancer recurrence.