Tag: immunotherapy

Categories : AllergiesTags :

Immunotherapy Lets Children with High-threshold Allergy Safely Eat Peanut Butter

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Photo by Corleto on Unsplash

Children with high-threshold peanut allergy who ate gradually larger doses of store-bought peanut butter achieved significantly higher and long-lasting rates of desensitisation compared to those who avoided peanuts, according to a new study led by researchers at the Icahn School of Medicine at Mount Sinai.  

Results of the trial appear in NEJM Evidence. 

“Our study results suggest a safe, inexpensive and effective pathway for allergists to treat children with peanut allergy who can already tolerate the equivalent of at least half a peanut, considered a high-threshold peanut allergy,” said Scott Sicherer, MD, director of a food allergy institute at Mount Sinai and lead author of the paper. “Our findings open the gateway to personalised threshold-based treatments of food allergy and will encourage additional studies that delve deeper into peanut and other foods for this approach that might be a game-changer for the majority of people with food allergies.”   

The most common approach to a food allergy is to avoid the food, but in recent years peanut oral immunotherapy – medically supervised, very gradual daily feeding of increasing amounts of pharmaceutical-grade peanut protein – has become an option for individuals with peanut allergies.. However, studies that led to Food and Drug Administration approval of an injected biologic and oral peanut immunotherapy have specifically focused on people who react to very small amounts of food allergens, such as half a peanut or less (considered a low-threshold peanut allergy).

“Years ago, when people with milk and egg allergies were advised to undertake strict avoidance, our team initiated studies that found most people with milk and egg allergies could tolerate these foods in baked goods, which changed the global approach to these allergies,” said Julie Wang, MD, Professor of Pediatrics at the Icahn School of Medicine, clinical researcher at the Jaffe Food Allergy Institute, and co-senior author of the paper. “The research team recognised that more than half of people with peanut allergy can tolerate half a peanut or more, and thought that this group of people might be treatable if we took a different approach to peanut oral immunotherapy. We were thrilled to find that this treatment strategy was even more successful than we had anticipated.”  

To test this hypothesis, the study team recruited 73 children ages 4 to 14 years old. Study participants were assigned, at random, to either test the new treatment strategy or continue avoiding peanuts. The children in the peanut-ingestion group began with a minimum daily dose of 1/8 teaspoon of peanut butter and gradually increased their dose every eight weeks over the course of 18 months, ending at one tablespoon of peanut butter or an equivalent amount of a different peanut product. All dose increases took place under medical supervision. None of the study participants in the peanut-ingestion group had severe reactions or needed epinephrine during home dosing  and only one received epinephrine during a supervised dosing visit.  

Following the treatment regimen, children from the peanut-consuming cohort participated in a feeding test, carefully supervised by the study team, to evaluate how much peanut they could eat without an allergic reaction. All 32 children from the peanut-consuming group who participated in the feeding test could tolerate the maximum amount of 9 grams of peanut protein, or three tablespoons of peanut butter. By contrast, only three of the 30 children from the avoidance group who underwent the feeding test after avoiding peanuts for the duration of the study could tolerate this amount.  

Because the trial took place during the COVID-19 pandemic and some families preferred avoiding close encounters indoors, some did not return to the study site for the feeding test. Using a common statistical technique to account for the children who missed the feeding test, the team reported that 100 percent of the ingestion group and 21 percent of the avoidance group tolerated an oral food challenge that was at least two doses more than they could tolerate at the beginning of the study.  

To test if the response to treatment was durable, children in the peanut-ingestion group who could tolerate nine grams of protein during the feeding test went on to consume at least two tablespoons of peanut butter weekly for 16 weeks and then avoided peanuts entirely for eight weeks. Twenty-six of the 30 treated children who participated in a final feeding test after the eight-week abstinence period continued to tolerate nine grams of peanut protein, indicating that they had achieved sustained unresponsiveness to peanuts. The three participants from the avoidance group who could eat nine grams of peanut protein without reaction at the earlier food test were considered to have developed natural tolerance to peanuts. A comprehensive analysis of data collected from all 73 study participants revealed that 68.4 percent of the peanut-ingestion group achieved sustained unresponsiveness, while only 8.6 percent of the avoidance group developed a natural tolerance.   

“These study results are very exciting and a huge step forward in personalizing food allergy treatment,” concluded Dr. Sicherer, the Elliot and Roslyn Jaffe Professor in Pediatric Allergy and Immunology at Mount Sinai. “My hope is that this study will eventually change practice to help these children and encourage additional research that includes this approach for more foods.”  

In addition to expanding the work to more foods and validation studies of their approach, the Mount Sinai study team aims to determine a better way of identifying individuals with higher thresholds, because the best way to do so currently requires a feeding test that is bound to cause an allergic reaction.  

Source: The Mount Sinai Hospital / Mount Sinai School of Medicine

Categories : CancerTags :

New Combination Immunotherapy for Melanoma and Breast Cancer

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3D structure of a melanoma cell derived by ion abrasion scanning electron microscopy. Credit: Sriram Subramaniam/ National Cancer Institute

A research team at the Medical University of Vienna led by Maria Sibilia has investigated a new combination therapy against cancer. This therapy employs systemic administration of the tissue hormone interferon-I combined with local application of Imiquimod. Promising results were seen in topically accessible tumours like melanoma and breast cancer models: the therapy led to the death of tumour cells at the treated sites and simultaneously activated the adaptive immune system to fight even distant metastases. The findings, published in Nature Cancer, could improve the treatment of superficial tumours such as melanoma and breast cancer.

In recent years, immunotherapies have had significant success in the treatment and cure of a wide range of cancers. However, for some patients, these agents are still not sufficiently effective. As part of a preclinical study, Maria Sibilia, Head of the Center for Cancer Research at the Medical University of Vienna, therefore investigated the effects of a combination immunotherapy consisting of systemic administration of the tissue hormone interferon (IFN)-I and local imiquimod therapy. Imiquimod is an active substance that activates the innate receptors TLR7/8 and used to treat basal cell carcinomas. The researchers employed various preclinical mouse tumour models of melanoma and breast cancer. What both tumours have in common is that they are accessible to local therapy and often form distant metastases.

Effective for local tumours and distant metastases

Immunotherapies use the body’s own immune system to fight cancer cells. Plasmacytoid dendritic cells (pDCs), which are activated by Imiquimod via TLR7/8, play an important role in this process. The study showed that oral imiquimod stimulates pDCs to produce the tissue hormone IFN-I. This sensitised other dendritic cells and macrophages in the tumour environment to topical imiquimod therapy, which inhibited the formation of new blood vessels via the cytokine IL12 leading to the death of tumour cells.
The combination immunotherapy not only had an effect on the treated tumours, but also on distant metastases. It reduced the formation of new metastases thus preventing tumour relapses and increasing the sensitivity of melanomas to checkpoint inhibitors.

“These findings illustrate that the combination of systemic treatment with imiquimod or IFN-I and topical therapy with imiquimod has the potential to expand treatment options for patients and improve therapy outcomes in locally accessible tumors such as melanoma or breast cancer,” emphasizes Maria Sibilia.
“Topical treatment of the primary tumor with imiquimod is essential for this combination therapy with systemic IFN-I to be effective at the treated site and also to clear distant metastases,” adds Philipp Novoszel, MedUni Vienna, one of the first authors of the study.

The results suggest that this therapeutic strategy has the potential to improve treatment outcomes in superficial and thus locally accessible tumors such as melanoma and breast cancer – on the one hand through therapy-associated cancer cell death at the locally treated tumors, but also through the induction of a T cell-induced anti-tumor immune response at distant metastases, which is further enhanced by checkpoint inhibitors.

“Our aim is to continue developing immunotherapeutic strategies in order to improve the long-term prospects for patients who are not yet responding well to these agents,” says Maria Sibilia, who is also Deputy Head of the Comprehensive Cancer Center of MedUni Vienna and University Hospital Vienna.
“As systemic interferon is a well-known cancer therapy and dendritic cells are activated in a similar way to our preclinical models, we believe that the new combination therapy can show an effect in patients,” adds Martina Sanlorenzo, dermato-oncologist at MedUni Vienna and co-first author of the study.

Publication: Nature Cancer
Systemic IFN-I combined with topical TLR7/8 agonists promotes distant tumor-suppression by c-Jun-dependent IL-12 expression in dendritic cells
Sanlorenzo M, Novoszel P, Vujic I, Gastaldi T, Hammer M, Fari O, De Sa Fernandes C, Landau AD, Göcen-Oguz BV, Holcmann M, Monshi B, Rappersberger K, Agnes Csiszar A, Sibilia M
DOI: 10.1038/s43018-024-00889-9; https://www.nature.com/articles/s43018-024-00889-9

Source: Medical University of Vienna

Categories : Cancer Cardiovascular DiseaseTags :

How Checkpoint Immunotherapy also Increases the Risk of Cardiovascular Disease

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Source: Wikimedia CC0

Cancer immunotherapy is known to also make patients more vulnerable to heart attack and stroke. A new study led by researchers at NYU Langone Health points to a possible explanation for this side effect: the treatment interferes with immune regulation in the heart’s largest blood vessels.

This new work focused on immune checkpoint inhibitors, which work by blocking molecules embedded on the surface of cells – immune checkpoints – which normally serve as “brakes” that prevent excess immune activity, or inflammation. Some tumours are known to hijack these checkpoints to weaken the body’s defences, so by blocking the checkpoints, the treatments enable the immune system to kill tumour cells.

Unfortunately, this treatment type may also trigger damaging levels of inflammation in the heart, brain, stomach, and other organs, the researchers say. For example, past studies have shown that about 10% of those with atherosclerosis have a heart attack or stroke following cancer treatment. Until now, the specific mechanisms behind this issue had remained unclear.

To address this question, the research team explored at a cellular level how immune checkpoint inhibitors interact with immune cells within arterial plaques. A genetic analysis by the study authors showed that the same type of immune checkpoints targeted by cancer therapies also appear in arterial immune cells, establishing a link between checkpoint inhibitors and cardiovascular events.

“Our findings provide new insight into how a drug intended to target tumours can also prompt a heightened immune response in arteries and increase risk of heart disease,” said study co-senior author Chiara Giannarelli, MD, PhD. “Cancer patients and their physicians should be aware that they may need to monitor for new heart concerns following cancer treatment,” added Dr Giannarelli.

For the current study, published in Nature Cardiovascular Research, the researchers analysed the genetic activity of thousands of immune cells collected from the plaques of 50 men and women undergoing a surgical procedure to address atherosclerosis.

The investigators also explored how type 2 diabetes, a known risk factor for both cancer and heart disease, may make those with atherosclerosis even more vulnerable to the ill effects of checkpoint inhibitors, adds Dr Giannarelli, also an associate professor in the Department of Pathology at NYU Grossman School of Medicine. As part of the study, the team assessed immune checkpoint activity in arterial tissue collected from eight patients with diabetes and four healthy volunteers. Notably, none had a history of atherosclerosis. The results showed that the diabetes patients had less measurable communication between checkpoints, which in turn can prompt increased inflammation.

Other experiments further revealed that taking immune checkpoint inhibitors might make it harder to combat atherosclerosis. Under normal circumstances, physicians typically prescribe low-fat diets to reduce plaque buildup and inflammation. Indeed, the researchers’ experiments in rodents confirmed that such diets boost communication between immune checkpoints within arteries. However, cancer patients may be at a disadvantage because their therapy, by blocking these same checkpoints, may counteract the anti-inflammatory benefits of fat reduction.

“Our findings highlight how cancer, diabetes, and heart disease do not exist in a vacuum, and that it is critical to consider how targeting one of these conditions can affect the others,” said study co-senior author Kathryn J. Moore, PhD. “Now that experts have a better understanding of the interplay between these diseases, they can begin to explore new strategies to lower the risk of unintended health concerns caused by their treatment,” added Dr Moore. She cautions that the study did not directly assess immune checkpoint behaviour in cancer patients. The team plans to do so in future investigations, she adds.

Source: NYU Langone Health

Categories : Cancer NeurologyTags :

A Way to Make Glioblastoma Cells Visible to Immune Cells

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MRI scan showing brain cancer. Credit: Michelle Monje, MD, PhD, Stanford University

Patients with glioblastoma typically survive less than two years after diagnosis, even with cutting-edge therapies. The latest immunotherapies have been unsuccessful, likely because glioblastoma cells have few, if any, natural targets for the immune system to attack.

In a cell-based study, scientists at Washington University School of Medicine have forced glioblastoma cells to display immune system targets, potentially making them visible to immune cells and newly vulnerable to immunotherapies. The strategy involves a combination of two drugs, each already FDA-approved to treat different cancers.

The study is online in the journal Nature Genetics.

“For patients whose tumours do not naturally produce targets for immunotherapy, we showed there is a way to induce their generation,” said co-senior author Ting Wang, PhD, professor of medicine and Department of Genetics head at WashU Medicine. “In other words, when there is no target, we can create one. This is a very new way of designing targeted and precision therapies for cancer. We are hopeful that in the near future we will be able to move into clinical trials, where immunotherapy can be combined with this strategy to provide new therapeutic approaches for patients with very hard-to-treat cancers.”

To create immune targets on cancer cells, Wang has focused on stretches of DNA in the genome known as transposable elements. In recent years, transposable elements have emerged as a double-edged sword in cancer, according to Wang. His work has shown that transposable elements play a role in causing tumours to develop even as they present vulnerabilities that could be exploited to create new cancer treatment strategies.

For this study, Wang’s team took advantage of the fact that transposable elements naturally can cause a tumour to churn out random proteins that are unique to the tumour and not present in normal cells. Called tumour antigens or neoantigens, these unusual proteins could be the targets for immunotherapies, such as checkpoint inhibitors, antibodies, vaccines and genetically engineered T cell therapies.

Even so, some tumours, including glioblastoma, have few immune targets produced naturally by transposable elements. To address this, Wang and his colleagues, including co-senior author Albert H. Kim, MD, PhD, neurosurgery professor, have demonstrated how to purposely force transposable elements to produce immune system targets on glioblastoma cells that normally lack them.

The researchers used a combination of two drugs that influence the epigenome, which controls gene activation. When treated with the two epigenetic therapy drugs, the tightly packed DNA molecules of the glioblastoma cells unfurled, triggering transposable elements to begin making the unusual proteins that could be used to target the cancer cells. The two drugs were decitabine, which is approved to treat myelodysplastic syndromes, a group of blood cancers; and panobinostat, which is approved for multiple myeloma, a cancer of white blood cells.

Before investigating this strategy in people, the researchers are seeking ways to target the epigenetic therapy so that only the tumour cells are induced to make neoantigens. In the new study, the researchers cautioned that normal cells also produced targets when exposed to the two drugs. Even though normal cells didn’t produce as many neoantigens as the glioblastoma cells did, Wang and Kim said there is a risk of unwanted side effects if normal cells create these targets as well.

In ongoing work, Wang and Kim are investigating how to use CRISPR molecular editing technology to induce specific parts of the genome in cancer cells to produce the same neoantigens from transposable elements that are common across the human population. Such a strategy could give many patients’ tumours – even different cancer types – the same targets that could respond to the same immunotherapy, while sparing healthy cells. There are then multiple possible ways to go after such a shared target, including checkpoint inhibitors, vaccines, engineered antibodies and engineered T cells.

Source: Washington University School of Medicine

Categories : CancerTags :

Oestrogens are Implicated in More than Just Breast Cancers

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Photo by National Cancer Institute on Unsplash

Oestrogens are known to drive tumour growth in breast cancer cells that carry its receptors, but a new study by Duke Cancer Institute researchers unexpectedly finds that oestrogens play a role in fuelling the growth of breast cancers without the receptors, as well as numerous other cancers.

Writing in the journal Science Advances, the researchers describe how oestrogens not only decrease the ability of the immune system to attack tumours, but also reduce the effectiveness of immunotherapies that are used to treat many cancers, notably triple-negative breast cancers. Triple-negative breast cancers are an aggressive form of disease that are negative for oestrogen, progesterone, and the HER2 receptor proteins.

Informed by retrospective analysis of patient data and experiments in mice, the researchers found that anti-oestrogen drugs reversed the effects of oestrogens, restoring potency to immunotherapies.

“The treatment for triple-negative breast cancer has been greatly improved with the advent of immunotherapy,” said senior author Donald McDonnell, PhD, professor at Duke University School of Medicine.

“Developing ways to increase the anti-cancer activity of immunotherapies is a primary goal of our research,” McDonnell said. “Here we have found a simple way bolster the effectiveness of immunotherapy for this type of breast cancer and the benefit was even seen in other cancers, including melanoma and colon cancers.”

McDonnell and colleagues, including lead author Sandeep Artham, a postdoctoral associate in the McDonnell lab, focused on a type of white blood cell called eosinophils, which are typically activated during allergic reactions and inflammatory diseases.

Eosinophils have recently been identified as important in tumours, and a phenomenon called tumour associated tissue eosinophilia, or TATE, is associated with better outcomes among patients with multiple types of cancer, including colon, oesophageal, gastric, oral, melanoma and liver cancers.

In their studies, the Duke team described how oestrogens decrease the number of eosinophils and TATE in mice. The hormone contributes to increased tumour growth in oestrogen receptor-negative breast cancer tumours and in melanoma tumours, which do not rely on oestrogen receptors for tumour growth.

Conversely, anti-oestrogen therapies inhibited oestrogen receptor signalling and enhanced the efficacy of immunotherapies, slowing tumour growth.

“These findings highlight the importance of oestrogen-receptor signalling as a regulator of eosinophil biology and TATE and highlight the potential near-term clinical application of anti-oestrogen drugs to increase the benefits of immunotherapies in multiple tumour types,” McDonnell said.

He said clinical trials are being planned using an investigational anti-oestrogen drug called lasofoxifene among patients with triple-negative breast cancers.

Source: Duke University Medical Center

Categories : CancerTags :

Better Response to Lung Cancer Immunotherapy with Combination Treatment

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Lung cancer metastasis. Credit: National Cancer Institute

In research published in Nature Communications, scientists have tested a combination of treatments in mice with lung cancer and shown that these allow immunotherapies to target non-responsive tumours.

The study findings, from Francis Crick Institute, in collaboration with Revolution Medicines, show that targeting tumours in different ways simultaneously might increase response to treatments.

The scientists tested a combination of tool compounds in mice with lung cancer. These compounds were used to represent:

  • Targeted drugs which block a cancer-causing protein called KRAS G12C. These have been approved for use in lung cancer, but often fail to benefit patients in the long term because the tumours develop resistance to these medicines over time.
  • Immunotherapy drugs. These are designed to stimulate the immune system to fight the tumour, but only 20% of people with lung cancer respond, as tumours often block immune cells from entering.

The researchers combined a newly identified KRAS G12C inhibitor, with a compound that blocks a protein called SHP2, which inhibits cancer cells and can also activate tumor immunity.

These two inhibitors were combined with an immune checkpoint inhibitor, which blocks proteins that help the cancer cells hide from the immune system.

Source: Francis Crick Institute

Categories : Cancer Metabolic DisordersTags :

The Outcomes of Cancer Therapies and BMI Have a Complex Relationship

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Risk of mortality during cancer treatment in relation to BMI. For non-small cell lung cancer treatment, immunotherapy seems to pose less risk for persons under a certain BMI, while conventional chemotherapy appears optimal for persons who might be overweight or obese. Credit: Osaka Metropolitan University

While being overweight increases the risk of developing lifestyle-related diseases, there is a phenomenon known as the obesity paradox where a decreased risk of death has been seen during cancer therapy. However, that paradox might not hold true for all cancer therapies, an Osaka Metropolitan University team reports in JAMA Network Open, a publication of the American Medical Association.

Led by graduate student Mr Yasutaka Ihara and Professor Ayumi Shintani of the Graduate School of Medicine’s Department of Medical Statistics, the team used a Japanese administrative claims database of more than 500 000 lung cancer patients and examined the relation between body mass index (BMI) and the risk of mortality during immunotherapy and conventional chemotherapy.

Focusing only on patients with advanced non-small cell lung cancer, the team found that the higher the BMI, the lower the risk of mortality when undergoing both immunotherapy and chemotherapy, though it does a U-turn around a BMI of 24. Patients with a BMI under 28 showed lower risk of mortality when undergoing immunotherapy compared to conventional chemotherapy, but for those at or over that figure, the risk increases with immunotherapy while it continues to get lower with chemotherapy.

“Immunotherapy might not always be the optimal treatment method for obese patients with advanced non-small cell lung cancer, so the use of conventional chemotherapy should also be considered,” Mr. Ihara stated. “In addition to BMI, age, hormones, and gut microbiota have been reported as factors that influence the effectiveness of immunotherapy. Evaluation of whether immunotherapy or conventional chemotherapy improves survival in the presence of these factors is expected to contribute to the development of precision medicine.”

Source: Osaka Metropolitan University

Categories : Cancer Immune SystemTags :

How Cancer Reprograms Immune Cells to Join the Enemy

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Squamous cancer cell being attacked by cytotoxic T cells. Image by National Cancer Institute on Unsplash

Cancer has been described as “a wound that does not heal,” implying that the immune system is unable to wipe out invading tumour cells. A new discovery reported in PNAS confirms that a key molecule can reprogram immune cells into turncoats that promote cancer growth.

Studying the behaviour of these “pro-tumour” immune cells is important because they could be targets for therapies that block their harmful activity, said Minsoo Kim, PhD, corresponding author of the study and a research leader at the Wilmot Cancer Institute.

Kim led a team of scientists investigating the dynamic interactions that occur between cells in the tumor environment, and the underlying factors that cause the harmful transformation of immune cells from good to bad.

They found that PAF (platelet-activating factor) is the key molecule that controls the destiny of the immune cells. PAF not only recruits cancer-promoting cells, but it also suppresses the immune system’s ability to fight back. In addition, they found that multiple cancers rely on the same PAF signals.

“This is what could be most significant,” said Kim. “Because if we find a treatment that could interfere with PAF, it could potentially apply to many types of cancer.”

Much of the team’s work focused on pancreatic cancer cells. It is one of the most deadly cancers, with a five-year survival rate of about 12%, and is notoriously hard to treat because pancreatic tumours are surrounded by a toxic stew of proteins and other tissues that protect the cancer from the immune system’s natural role to attack invaders. They also studied breast, ovarian, colorectal, and lung cancer cells, using advanced 3D imaging technology to watch the behaviour of immune cells as they swarmed to the cancerous region.

Source: University of Rochester Medical Center

Categories : CancerTags :

Advanced Lung Cancer Mortality Plunged Since Standardisation of Immunotherapy

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The largest population-based study to date supports the survival benefits of immunotherapy for people with metastatic non–small cell lung cancer.

Squamous cancer cell being attacked by cytotoxic T cells. Image by National Cancer Institute on Unsplash

Since the first immunotherapy drug to boost the body’s immune response against advanced lung cancer was introduced in the United States in 2015, survival rates of patients with the disease have improved significantly. That’s the conclusion of a recent real-world study published by Wiley online in CANCER, a peer-reviewed journal of the American Cancer Society.

For the research, a team led by Dipesh Uprety, MD, FACP, of the Barbara Ann Karmanos Cancer Institute and the Wayne State University School of Medicine, analysed data from the National Cancer Institute Surveillance, Epidemiology, and End Results database, which compiles cancer-related data covering approximately 48% of the US population. The investigators’ analysis focused on non–small cell lung cancer (NSCLC), which accounts for up to 90% of all cases of lung cancer and is the leading cause of cancer-related death among both men and women in the United States.

In a comparison of 100 995 patients with metastatic NSCLC treated in 2015–2020 (after immunotherapy was deemed the standard of care) and 90 807 patients with metastatic NSCLC in the pre-immunotherapy era of 2010–2014, patients in the immunotherapy era were less likely to die from any cause. The overall survival rates at one, three, and five years were 40.1% versus 33.5%, 17.8% versus 11.7%, and 10.7% versus 6.8%. The median overall survival was eight months in patients in the immunotherapy era and seven months in those in the pre-immunotherapy era.

Similarly, patients treated after immunotherapy was available were less likely to die specifically from cancer than those treated before immunotherapy. The one-, three-, and five-year cancer-specific survival rates were 44.0% versus 36.8%, 21.7% versus 14.4%, and 14.3% versus 9.0%, with a median survival of 10 months versus eight months.

Survival rates remained significantly better in the immunotherapy era even after accounting for factors including age, sex, race, income, and geographical area.

“By utilizing a large national database, our study provided real-world evidence of the positive impact of immunotherapy in patients with lung cancer,” said Dr Uprety. The investigators stressed that additional studies are needed, however. “Immunotherapy provides long-term benefits. Since the durable benefits of immunotherapy are limited to a small subset of patients, future research should aim to optimize immunotherapy with new agents that can benefit a broader population,” said lead author Yating Wang, MD, of Ascension Providence Hospital.

Source: Wiley

Categories : CancerTags :

‘Potentially Game Changing’ Immunotherapy Trial for Colorectal Cancer

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Human colon cancer cells. Credit: National Cancer Institute

Results from a new trial indicate that immunotherapy could successfully be used to treat the most common form of colorectal cancer, also known as bowel cancer.

The findings of the new study, a phase 1 trial involving the immunotherapy drugs botensilimab and balstilimab, have been published in the journal Nature Medicine, and it is the first time that consistent and durable responses to immunotherapy have been reported in difficult-to-treat patients.

Co-authored by Professor Justin Stebbing of Anglia Ruskin University (ARU), who describes the results as “potentially game changing”, the study focused on the most common type of colorectal tumours, known as MSS mCRC, or microsatellite stable metastatic colorectal cancer.

Although immunotherapy has previously been shown to work on patients with specific mismatch repair deficient (dMMR) tumours, only a small percentage of colorectal cancer patients have this type of tumour, and immunotherapy has so far been ineffective in patients with more common MSS mCRC tumours.

The new study involved using the immunotherapy drug botensilimab in conjunction with balstilimab on a group of patients in the United States. These drugs are both monoclonal antibodies, which work by triggering the body’s immune system to attack the cancer.

Of the patients in the phase 1 trial, 101 took part in a six-month follow-up and of these, 61% of them saw their tumour shrink or remain stable after receiving a combination of botensilimab (BOT) and balstilimab (BAL). The most common side-effects, or treatment-related adverse events, were diarrhoea and fatigue.

Justin Stebbing, Professor of Biomedical Sciences at Anglia Ruskin University (ARU) and communicating author of the study, said:

“These results are incredibly exciting. Colorectal or bowel cancer is one of the most common forms of cancer worldwide and this is the first time there has been convincing evidence that immunotherapy can work in all forms of colorectal tumours, so this is potentially game changing.

“This is now progressing into later phase clinical trials and we hope the FDA in the United States approve its use very soon. And because this is such an important area, affecting so many people, we hope authorities in the UK are also able to move quickly.”
Joint first author Dr Andrea Bullock, Assistant Professor in Medicine at Beth Israel Deaconess Medical Center, said:

“This study sheds light on the potential of the BOT/BAL combination to treat microsatellite stable metastatic colorectal cancer, the most common form of colorectal cancer which has historically not responded to immunotherapy, and we hope our results will offer new hope for those diagnosed.”
Joint last author Dr Anthony El-Khoueiry, Associate Director of Clinical Research and Chief of Section of Developmental Therapeutics at the USC Norris Comprehensive Cancer Center, said:

“This phase 1 study of botensilimab highlights its promising anti-tumour activity that encompasses immunologically cold tumours such as MSS colorectal cancer. The efficacy noted highlights the potential of botensilimab through its broader engagement of anti-tumour immunity.”

The full open access paper, published in , is available here 

Source: Anglia Ruskin University