Tag: cancer treatment

Categories : CancerTags : Leave a comment

Vorasidenib Extends Progression-free Survival in Glioma Subtype

On By ModernMedia
Photo by National Cancer Institute on Unsplash

In a study published in the New England Journal of Medicine, scientists report that a new targeted therapy drug can extend progression-free survival for a subtype of glioma. The finding suggests a possible new treatment option for people with the slow-growing but deadly brain tumour.

The team, co-led by UCLA, found the drug vorasidenib more than doubled progression-free survival in people with recurrent grade 2 glioma with IDH1 and IDH2 mutations. Compared with placebo, those who took vorasidenib went for nearly 17 more months without their cancer worsening, delaying the time before they needed to begin chemotherapy and radiation.

The type of glioma studied in the paper, recurrent grade 2 glioma with IDH1 and IDH2 mutations, tends to affect younger people, often those in their 30s. The current standard treatment, a combination of radiation and chemotherapy, can cause neurological deficits that make it hard for patients in an often challenging and busy stage of life.

UCLA professor of neuro-oncology Dr Timothy Cloughesy, co-senior author of the study, said that the availability of a treatment that enables patients to go for longer periods of time between chemotherapy and radiation treatments could have a major impact.

“We’re always concerned about the delayed effects of radiation,” said Cloughesy. “Having the ability to hold off on getting radiation therapy to the brain with an effective therapy is really critical and very meaningful to this population of patients.”

Vorasidenib is a dual inhibitor of mutant IDH1/2, meaning that it prevents the formation and accumulation of the onco-metabolite 2-Hydroxyglutarate, or 2-HG, that occurs when genetically altered versions of two enzymes, IDH1 and IDH2, are present in a tumour. 2-HG is thought to be responsible for the formation and maintenance of IDH-mutant gliomas.

The study is also the first clinical trial to analyse a targeted therapy drug specifically developed to treat brain cancer. Targeted therapies focus on specific molecules that are involved in cancer cell growth and metastasis. Unlike chemotherapy and other therapies that can affect both cancerous and healthy cells, targeted therapies only attack cancer cells with the mutated target while sparing normal cells.

While there has been great progress in using targeted therapies to treat many types of cancer, the difficulty of crossing the blood-brain barrier makes developing targeted therapies for brain tumours challenging. Vorasidenib is a brain-penetrant inhibitor, allowing it to cross the blood-brain barrier.

The study involved 331 people aged 12 and older who had been diagnosed with recurrent grade 2 glioma with the IDH1 and IDH2 mutations and who had undergone brain tumour surgery. From that group, 168 were randomised to vorasidenib and 163 to placebo.

Among those who received vorasidenib, the disease did not progress for an average of 27.7 months, significantly longer than the 11.1 months for those who received the placebo. And among those who received vorasidenib, 85.6% went for 18 months before their next treatment, while 83.4% went for 24 months between treatments.

The disease progressed in just 28% of people receiving v orasidenib, compared to 54% of those receiving placebos. And as of September 2022, which was 30 months after the study began, 72% of patients who were in the vorasidenib group were still taking the drug and their disease had not progressed.

For patients who were originally in the placebo group whose cancer began to progress during the study, doctors permitted a switch to vorasidenib. The researchers observed limited adverse side effects from vorasidenib. “This is the first targeted treatment that shows unequivocal efficacy in this population and is precedent-setting for this disease,” Cloughesy said.

Source: University of California – Los Angeles Health Sciences

Categories : Cancer New Compounds and TreatmentsTags : Leave a comment

Momelotinib Trumps Standard Care in Treating Myelofibrosis

On By ModernMedia
Photo by Louise Reed on Unsplash

A Phase III trial testing the targeted therapy momelotinib showed that patients with myelofibrosis had clinically significant improvement in disease-related symptoms, including anaemia and spleen enlargement.

The findings, published in The Lancet, support the use of momelotinib over the standard therapy (danazol) in treating myelofibrosis patients that were resistant, refractory or intolerant to firstline therapy, especially symptomatic patients and those with anemia.

“Current options for managing anaemia in our myelofibrosis patients provide only modest and temporary benefits, so we are excited about these findings,” said study lead Srdan Verstovsek, MD, PhD, professor of Leukemia at University of Texas. “The trial results suggest that momelotinib is safe, well-tolerated and can improve one of the most common and debilitating clinical problems for this patient population.”

Myelofibrosis is an uncommon bone marrow cancer that is part of a group of diseases known as myeloproliferative neoplasms. A hallmark of the disease is dysregulated JAK signalling, which disrupts blood cell production and leads to symptoms including an enlarged spleen and anaemia. Chronic anaemia in these patients is associated with poor prognoses.

Currently approved JAK inhibitors can improve spleen responses and other disease-related symptoms, but they also can worsen anaemia. In this trial, momelotinib improved anaemia and reduced transfusion dependency in myelofibrosis patients previously treated with a JAK inhibitor. Momelotinib, a potent ACVR1/ALK2 and JAK1/2 inhibitor, can be administered and maintained at full dose because it does not suppress bone marrow activity like other JAK inhibitors.  

The randomised Phase III MOMENTUM trial was designed to compare the clinical benefits of momelotinib to danazol, a synthetic androgen currently used to treat anaemia in symptomatic myelofibrosis patients.

The trial enrolled 195 adult patients (63% male, 37% female) from 107 research sites across 21 countries. Trial participants were randomised (2:1) to receive momelotinib plus placebo or danazol plus placebo. A significantly greater proportion of patients who received momelotinib saw benefits in their disease symptoms (25%) compared to those receiving danazol (9%).

Patients treated with momelotinib also experienced a significant reduction in their spleen size, with 25% responding after 24 weeks of therapy. Additionally, these patients required fewer blood transfusions compared to those receiving danazol.

The safety profile of momelotinib was comparable to previous clinical trials. The most common non-haematological side effects experienced by trial participants in the momelotinib group included diarrhoea, nausea, weakness and itching or irritated skin.

“If approved, momelotinib could offer an effective option for patients with myelofibrosis to improve anemia, splenomegaly and other disease-related symptoms over other approved medications so far,” Verstovsek said. “Momelotinib may also be an ideal partner for combinations with other investigational agents in development to further control myelofibrosis symptoms.”

Patient follow-up is ongoing and long-term survival continues to be monitored.

Source: University of Texas MD Anderson Cancer Center

Categories : CancerTags : Leave a comment

Turning a Traditional Chinese Medicinal Plant into a Cancer Fighter

On By ModernMedia
Photo by Bundo Kim on Unsplash

The evolutionary secrets that enable the traditional Chinese medicinal herb known as barbed skullcap to produce cancer fighting compounds have been unlocked by a collaboration of UK and Chinese researchers, who published their research in the journal Molecular Plant.

The researchers used DNA sequencing technology to assemble the genomic sequence of skullcap (Scutellaria barbata) known in China as banzhilian. This gave researchers the genetic information, a microevolutionary history, required to identify how the plant produces the compound scutebarbatine A, which acts against a range of cancer cells.

Professor Cathie Martin, Group Leader at the John Innes Centre, and one of the authors of the study said, “We have found that the primary metabolite has activity against cancer cells but not non-cancer cells which is especially important for an anti-cancer metabolite. Now we are looking to develop synthetic methods for producing more of the lead compound.”

In Traditional Chinese Medicine (TCM), to isolate medicinal chemistry from the plant, the herb is boiled in water for two hours and extract is dried to produce a powder and taken as a decoction (concentrated liquid). Now, with the knowledge of the genes that make up the biochemical pathway behind the anti-cancer activity of the herb, researchers are close to being able to synthesise larger quantities of compounds more rapidly and sustainably by using a host such as yeast.

The research is led by CEPAMS, a partnership between the John Innes Centre and the Chinese Academy of Science and supported by The Royal Society.

“This is a fantastic collaboration about developing interesting drug leads from natural resources and shows the practical value of focusing on the microevolution of a species” said Professor Martin.

The Skullcap genus has been used for centuries in TCM for treatment of different medical conditions. Clinical work has shown that preparations based on Scutellaria barbata during chemotherapy can reduce the risk of metastatic tumours.

CEPAMS Group Leader based at Shanghai Dr Evangelos Tatsis said, “Natural products have long been the lead compounds for the discovery of new drugs. By following the trail of the traditional Chinese plants, we can develop new anti-cancer medicines and this research marks a crucial step in that direction.”

Plant-based traditional medicines have long been used to provide leads for the new drug discovery, leading to drugs such as vinblastine and taxol which are now used clinically as anticancer drugs.

TCM is one of the best catalogued systems with empirical information about the therapeutic properties of herbal remedies.

Anti-cancer drugs obtained from traditional Chinese medicine have higher efficacy than chemical synthetic drugs and with less toxic side effects. The genomes of medicinal skullcaps reveal the polyphyletic origins of clerodane diterpene biosynthesis in the family Laminiaceae, is published in Molecular Plant

Source: John Innes Centre

Categories : Cancer Cardiovascular DiseaseTags : Leave a comment

Study Identifies Risk Factors for CVD among Young Cancer Survivors

On By ModernMedia
Source: Pixabay CC0

Adolescent and young adult (AYA) cancer survivors are at risk of experiencing treatment-related effects later in life, including cardiac damage. New research published in in CANCER has identified a number of sociodemographic and modifiable risk factors linked to these patients’ risk of developing cardiovascular disease (CVD).

The study by investigators at Duke University and The University of Texas MD Anderson Cancer Center relied on 2009–2018 data from the National Health Interview Survey, which collects information on a broad range of health topics through personal interviews of US households. Responses from 4766 AYA cancer survivors and 47 660 controls (without a history of cancer) were included. 

The risk of CVD was significantly higher in survivors than controls by sex, race/ethnicity, income, education, smoking status, and physical activity.

In the AYA survivor population, male sex, Black race, household income under $50 000 a year, and current or former smoking were all associated with higher odds of CVD. Household income < $50 000 a year disproportionately increased the odds of CVD in survivors compared with controls.  Performing any moderate to vigorous intensity physical activity was associated with lower CVD odds.  

“These results highlight the importance of long-term surveillance of AYAs after cancer treatment to ensure that appropriate screenings are initiated to reduce the risk of CVD and to promote healthy behavioural changes, such as physical activity, which impact long-term CVD outcomes,” said lead author Amy Berkman, MD, of the Duke University School of Medicine. 

Source: Wiley

Categories : CancerTags : Leave a comment

Immunotherapy Flop Leads to Cancer Treatment Breakthrough

On By ModernMedia
Human B cell
Scanning Electron Micrograph of a human B Cell. Credit: NIH

When patients in the UK showed adverse side effects during a cancer immunotherapy trial, researchers went back through the data and worked with patient samples to see what went wrong. Published in Nature, their findings provide clues into the dangerous side effects of many immunotherapies – and point to a better strategy for treating solid tumours.

“This work shows the importance of learning from early stage clinical trials,” says La Jolla Institute for Immunology (LJI) Professor Pandurangan Vijayanand, MD, PhD, who co-led the new research with Christian H. Ottensmeier, MD, PhD, FRCP, a professor with the University of Liverpool.

“In the oncology world, immunotherapy has revolutionised the way we think about treatment,” said Prof Ottensmeier. “We can give immunotherapies to patients even with metastatic and spreading disease, and then just three years later wave goodbye and tell them their cancer is cured. This is an astounding change.”

Unfortunately, only 20–30% of solid cancer patients given immunotherapies go into long-term remission. Some people see no change after immunotherapy, but others develop serious side effects, which can be debilitating, even fatal, and these patients are forced to discontinue the immunotherapy.

The researchers worked with samples from a recent UK clinical trial for head and neck cancers. The patients were given an oral cancer immunotherapy – a PI3Kδ inhibitor. At the time, PI3Kδ inhibitors had proven effective for B cell lymphomas but had not yet been tested in solid tumours.

PI3Kδ inhibitors are a new to cancer immunotherapy, but they hold promise for their ability to inhibit ‘regulatory’ T cells (Tregs). Tregs normally try to stop other T cells, called effector T cells, from targeting the body’s own tissues. Oncologists inhibit Tregs inside tumours so effector T cells can let loose and generate cancer-killing CD8+ T cells.

“Having an oral tablet that can take off the brakes – the Tregs– can be a great asset for oncologists,” said Prof Vijayanand.

Unfortunately, 12 of the 21 patients in the trial had to discontinue treatment early because they developed inflammation in the colon, a condition called colitis. “We thought this drug wouldn’t be toxic, so why was this happening?” said Prof Vijayanand.

Simon Eschweiler, PhD, an instructor at La Jolla Insitute, led the review into exactly how PI3Kδ inhibitor treatment affected immune cells in these patients. Gene sequencing showed that in the process of increasing tumour-fighting T cells in tumours, the PI3Kδ inhibitor also blocked a specific Treg cell subset from protecting the colon. Without Tregs patrolling there, pathogenic T cells, called Th17 and Tc17 cells, moved in and caused inflammation and colitis.

It was clear that a larger than needed PI3Kδ inhibitor dose had been given, and had disrupted the immune cell balance in the gut.

The pathway that leads to the toxicity seen in the new study may be broadly applicable to other organs harbouring similar Treg cells, and to other Treg cell-targeting immunotherapies like anti-CTLA-4, Eschweiler says.

The team found that intermittent dosing could be a valid treatment strategy that combines sustained anti-tumour immunity with reduced toxicity. The researchers are now designing a human clinical trial to test the intermittent dosing strategy in humans.

Why the lack of toxicity in trials for B cell lymphomas? Dr Eschweiler noted that in previous studies, lymphoma patients had been given several prior therapies leading to an overall immunocompromised state. This means the lymphoma patients didn’t have the same type or magnitude of immune response upon PI3Kδ inhibition. Meanwhile, the head and neck cancer patients were treatment-naive. Since their immune system was uncompromised, the immune-related adverse events were more rapid and pronounced.

Overall, the new study shows the importance of studying not just personalised therapies but personalised therapy doses and schedules.

Source: La Jolla Institute

Categories : CancerTags : Leave a comment

Capsaicin Sustained Release Formations – a Spicy Anti-cancer Treatment?

On By ModernMedia

A study published in Pharmacology & Therapeutics provides the first in-depth description of the anti-cancer activity of capsaicin sustained release formulations. Capsaicin, responsible for the hot and spicy taste of chili peppers, is being, explored in sustained release formulations of capsaicin for extended anti-cancer activity. However, how to get around its fiery taste remains a challenge.

The article chronicles the growth-suppressive activity of sustained release capsaicin drugs, including solid dispersion systems, liposomes, phospholipid complexes and nanoparticles. This marks the first publication to provide an in-depth description of the anti-cancer activity of capsaicin sustained release formulations. The research team was led by Associate Professor of Biomedical Sciences Piyali Dasgupta, PhD., and Professor of Biomedical Sciences Monica Valentovic, PhD.

“This review article is the first to provide a comprehensive overview of capsaicin formulations in human cancer,” said Prof Dasgupta, the study’s corresponding author. “Previous publications in the literature only briefly address sustained release formulations of capsaicin.”

The reviewers found that capsaicin displayed robust growth-inhibitory activity in a diverse array of human cancers. However, the clinical applications of capsaicin as a viable anti-cancer agent were hindered by three factors: poor solubility, low bioavailability and spicy flavour.

“Oral use of capsaicin is associated with unfavourable side effects such as stomach cramps, nausea, a burning sensation in the gut and gastrointestinal irritation,” said Prof Valentovic, a senior author on the publication. “A strategy to overcome these drawbacks is the development of different delivery systems, such as encapsulating capsaicin in long-acting sustained release drug delivery systems could allow for more consistent capsaicin levels that could be more efficient as anti-cancer agents.”

Source: Marshall University

Categories : Antibiotics CancerTags : Leave a comment

Unlikely Allies: Bacteria can Promote Cancer Metastasis

On By ModernMedia
Scanning Electron Micrograph of a breast cancer cell. Credit: NIH

Researchers have found that bacteria lurking inside tumours promote cancer metastasis. They do so by enhancing the strength of host cells against mechanical stress in the bloodstream, promoting cell survival during tumour progression, researchers report in the journal Cell.

“Our study reveals that the cancer cell’s behaviour is also controlled by the microbes hiding inside tumours, the majority of which were originally thought to be sterile,” said senior author Shang Cai of the Westlake Laboratory of Life Sciences and Biomedicine. “This microbial involvement is distinct from the genetic, epigenetic, and metabolic components that most cancer drugs target.”

“However, our study does not mean that using antibiotics during cancer treatment will benefit patients,” he cautioned. “Therefore, it is still an important scientific question of how to manage the intratumor bacteria to improve cancer treatment in the future.”

It is known that microbes play a critical role in affecting cancer susceptibility and tumour progression, particularly in colorectal cancers. New evidence suggests however that, in a broad range of cancer types, they also form integral components of the tumour tissue itself, such as pancreatic cancer, lung cancer, and breast cancer. Microbial features are linked to cancer risk, prognosis, and treatment responses, yet the biological functions of tumour-resident microbes in tumour progression remain unclear.

Whether these microbes are actually drivers of tumour progression has been an intriguing question. “Tumour cells hijacked by microbes could be more common than previously thought, which underscores the broad clinical value of understanding the exact role of the tumour-resident microbial community in cancer progression,” Cai explained.

To find answers, Cai’s team utilised a mouse model of breast cancer with significant amounts of bacteria inside cells, similar to human breast cancer. The bacteria were found to be capable of travelling through the circulatory system with the cancer cells, playing critical roles in tumour metastasis. These passenger bacteria have the capacity to modulate the cellular actin network, promoting cell survival against mechanical stress in circulation.

“We were surprised initially at the fact that such a low abundance of bacteria could exert such a crucial role in cancer metastasis. What is even more astonishing is that only one shot of bacteria injection into the breast tumour can cause a tumour that originally rarely metastasises to start to metastasise,” Cai said. “Intracellular microbiota could be a potential target for preventing metastasis in broad cancer types at an early stage, which is much better than to have to treat it later on.”

While intratumour bacteria was found to have a clear role in promoting cancer cell metastatic colonisation, the authors did not exclude the possibility that the gut microbiome and immune system may act together with intratumour bacteria to determine cancer progression. Future in-depth analyses of how bacteria invade tumour cells, how intracellular bacteria are integrated into the host cell system, and how bacteria-containing tumor cells interact with the immune system will help inform how to properly deploy antibiotics in cancer treatment.

Source: ScienceDaily

Categories : CancerTags : Leave a comment

‘A-Maize-ing’ Nanoparticles Target Cancer Cells Directly

On By ModernMedia
Computer=generated depiction of nanoparticles

Researchers have recently developed novel nanoparticles derived from maize that can target cancer cells directly, via an immune mechanism. The results of this study, published in Scientific Reports, are encouraging, and the technique has demonstrated efficacy in treating tumour-bearing laboratory mice with no adverse effects.

Nanoparticles, or particles whose size varies between 1 and 100nm, have shown tremendous potential in many areas of science and technology, including therapeutics. However, conventional, synthetic nanoparticles are complicated and expensive to produce and alternatives such as extracellular vesicles (EVs) have mass production challenges.
Another recently emerging option is that of plant-derived nanoparticles (NPs), which can be easily produced in high levels at relatively lower costs. Like EVs, these nanoparticle-based systems also contain bioactive molecules, including polyphenols (which are known antioxidants) and microRNA, and they can serve as vehicles for targeted drug delivery.

Recently, researchers from the Tokyo University of Science (TUS) developed anti-cancer bionanoparticles, using corn (maize) as the raw material.
Lead researcher Professor Makiya Nishikawa explained: “By controlling the physicochemical properties of nanoparticles, we can control their pharmacokinetics in the body; so, we wanted to explore the nanoparticulation of edible plants. Maize, or corn, is produced in large quantities worldwide in its native form as well as in its genetically modified forms. That is why we selected it for our study.” 

The team centrifuged a super-sweet corn juice and then filtered it through a syringe filter with a 0.45μm pore size, then ultracentrifuged to obtain NPs derived from corn. The corn-derived NPs (cNPs) were approximately 80nm in diameter with a tiny net negative charge of -17mV.

The research team then set up experiments to see whether these cNPs were being taken up by various types of cells. In a series of promising results, the cNPs were taken up by multiple types of cells, including the clinically relevant colon26 tumor cells (cancer cells derived from mice), RAW264.7 macrophage-like cells, and normal NIH3T3 cells. RAW264.7 cells are commonly used as in vitro screens for immunomodulators.

The results were astounding: of the three types of cells, cNPs only significantly inhibited the growth of colon26 cells, indicating their selectivity for carcinogenic cell lines. Moreover, cNPs were able to successfully induce the release of tumour necrosis factor-α (TNF-α) from RAW264.7 cells. TNFα is primarily secreted by macrophages, natural killer cells, and lymphocytes, which help mount an anticancer response. “The strong TNFα response was encouraging and indicated the role of cNPs in treating various types of cancer,” explains Dr. Daisuke Sasaki, first author of the study and an instructor and researcher at TUS.

A luciferase-based assay revealed that the potent combination of cNPs and RAW264.7 cells significantly suppressed the proliferation of colon26 cells. Finally, the research team studied the effect of cNPs on laboratory mice bearing subcutaneous tumours. Once again, the results were astonishing: daily injections of cNPs into colon26 tumours significantly suppressed tumour growth, without causing serious side effects, or weight loss.

“By optimising nanoparticle properties and by combining them with anticancer drugs, we hope to devise safe and efficacious drugs for various cancers,” observed an optimistic Prof Nishikawa.

Source: Tokyo University of Science

Categories : Cancer New Compounds and TreatmentsTags : Leave a comment

The Search for New Cancer Therapies Strikes Gold

On By ModernMedia
Photo by Jingming Pan on Unsplash

The gold complex auranofin has traditionally been used for treating rheumatism but is also being evaluated as a one number of new cancer therapies. According to a study published in Redox Biology, molecules with the same inhibition effect have been discovered that have a more specific effect than auranofin and therefore may have greater potential as cancer therapies.

Auranofin (AF) is classed by the WHO (World Health Organization) as an anti-rheumatic agent and is an active component in the drug Ridaura. AF is also currently being assayed in a string of clinical trials as a possible cancer therapy. One reason for the researchers’ interest in AF is its ability to inhibit thioredoxin reductase (TrxR), a protein central to the thioredoxin system, which protects cells from oxidative stress in all mammals. 

However, TrxR also protects cancer cells, making cancer therapies less effective. Moreover, TrxR, which affects cellular growth and survival, is upregulated in certain forms of cancer.

“There’s a great deal of interest in the ability to inhibit the thioredoxin system in the treatment of cancer, but there’s a risk that healthy cells will also be damaged and killed,” says the study’s co-last author Elias Arnér, professor at the Department of Medical Biochemistry and Biophysics at Karolinska Institutet. “Our aim is for TrxR inhibitors to be as specific as possible.”

The researchers studied the effects of AF in mouse cancer cells (lung adenocarcinoma and melanoma) and compared them with other recently-developed TrxR-inhibiting molecules called TRi-1 and TRi-2 (thioredoxin reductase inhibitors 1 and 2). 

The study, which was based on new proteomic methods of analysing the entire set of proteins in cells, suggests that the TRi compounds are more specific in their effect than AF. The results show that AF causes very high levels of oxidative stress and has other effects that seem unrelated to the inhibition of TrxR. They also demonstrate that TRi-1 seems to be the most specific TrxR inhibitor so far.

“Our results can serve as an important blueprint for further studies of AF’s mechanism of action and side effects,” said the study’s other co-last author Roman Zubarev, professor at the Department of Medical Biochemistry and Biophysics, Karolinska Institutet. “Having now compared AF with the more specific molecules TRi-1 and TRi-2, we hope that our findings will contribute to the further development of TrxR inhibitors as anticancer drugs.”

Source: Karolinska Insitutet

Categories : Cancer Diseases, Syndromes and ConditionsTags : Leave a comment

Treating Cancer with the Toxoplasma Gondii Parasite

On By ModernMedia
Source: National Cancer Institute on Unsplash

Scientists have discovered that Toxoplasma gondii, a parasite known to cause illness in pregnant women and immunocompromised patients, could potentially enhance the treatment of various types of tumours.

The parasite Toxoplasma gondii is a single-celled opportunistic protozoan capable of infecting a broad range of warm-blooded animals and has been reported in nearly one-third of the world’s human population. It has a number of health effects, including a strong link to schizophrenia and has even been associated with increased suicide attempts in mothers.

While many treatments have been able to treat tumours and prolong the lives of patients, there is a need to further enhance these. In the study, published in the Journal for ImmunoTherapy Cancer, scientists found that the commonly found parasite  is able to sensitise ‘cold’  tumours, that is, tumours unlikely to trigger a strong immune response, to immune checkpoint blockade therapy.

The researchers believe that this finding could have broader therapeutic implications for many types of cancers.

T. gondii has to live inside the cells of its host and secretes numerous proteins to counter the host’s immune defences and to facilitate their own invasion and colonisation of the host cells. The researchers first built a T. gondii mutant strain with limited growth and disease-causing ability, but which is also able to manipulate the host immune system.

By directly injecting this mutant parasite into solid tumours, it induces inflammatory responses in those tumours and even in tumours located in a distant location in the mouse body. The researchers further demonstrated that this treatment approach has made tumours more responsive to treatment with immune checkpoint inhibitors.

This dual treatment significantly extended the survival of mice and reduced tumour growth in mouse models of melanoma, Lewis lung carcinoma, and colon adenocarcinoma.

Dr Hany Elsheikha, Associate Professor in the School of Veterinary Medicine and Science at the University of Nottingham, and one of the lead authors of the study, said: “The use of a mutant version of Toxoplasma gondii in the treatment of certain tumours in mice models has been previously reported. What makes this study different is the confirmation that intratumoural injection with mutant Toxoplasma gondii strain boosts antitumour immunity and the effectiveness of checkpoint inhibition therapy.

“These are significant findings and are relevant to future tumour therapy. The marked reduction in tumour size and the significant improvement in the survival of mice that received this novel combinational therapy is promising but should be interpreted with caution as further research is needed.”

Source: University of Nottingham