Revolutionary Cancer Vaccine Trials Inspired by COVID Jab Begin

The team behind the OxfordAstraZeneca COVID-19 vaccine have used the same techniques to create a vaccine that could potentially ‘revolutionise’ cancer treatment.The researchers have designed a two-dose cancer vaccine using the same viral vector technology used in the Oxford COVID vaccine to increase the levels of anti-tumour T cells and shrink tumours in mice. The vaccine targets specific structures, known as MAGE proteins, found on the surface of many cancers.

We knew from our previous research that MAGE-type proteins act like red flags on the surface of cancer cells to attract immune cells that destroy tumours. MAGE proteins have an advantage over other cancer antigens as vaccine targets since they are present on a wide range of tumour types,” said Benoit Van den Eynde, Professor of Tumour Immunology at the University of Oxford.

This broadens the potential benefit of this approach to people with many different types of cancer. “Importantly for target specificity, MAGE-type antigens are not present on the surface of normal tissues, which reduces the risk of side-effects caused by the immune system attacking healthy cells.”

When combined with existing anti-PD-1 immunotherapy treatments, the vaccine showed a greater reduction in tumour size and improved the survival of the mice. Anti-PD-1 immunotherapy is a promising method of cancer treatment that works by ‘taking the brakesoff anti-tumour T cells and inciting them to kill cancer cells. However, it has so far proven to be largely ineffective thanks in part to the low levels of T cells in the majority of cancer patients.

This is where the tech borrowed from the Oxford-AstraZeneca vaccine comes in – a two-dose treatment can help to boost the levels of cancer-fighting CD8+ T cells. “Our cancer vaccines elicit strong CD8+ T cell responses that infiltrate tumours and show great potential in enhancing the efficacy of immune checkpoint blockade therapy and improving outcomes for patients with cancer,” said Prof Adrian Hill, Director of the Jenner Institute, University of Oxford.”

The team now plan to begin their first human clinical trial of the vaccine used in combination with anti-PD-1 immunotherapy in 80 patients with non-small cell lung cancer later this year as part of a collaboration between Vaccitech Oncology Limited (VOLT) and Cancer Research UK’s Centre for Drug Development. “This new vaccine platform has the potential to revolutionise cancer treatment. The forthcoming trial in non-small cell lung cancer follows a Phase 2a trial of a similar cancer vaccine in prostate cancer undertaken by the University of Oxford that is showing promising results,” said Hill.

Source: https://www.ox.ac.uk/
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https://www.sciencefocus.com/

Aggressive cancers in ‘evolutionary arms race’ with the immune system

Aggressive and highly-mutated cancers are engaged in an “evolutionary arms race” with the immune system, new research suggests. Gullet and stomach cancers with faults in their systems for repairing DNA build up huge numbers of genetic mutations which make them resistant to treatments like chemotherapy. But these numerous mutations mean they appear foreign to the immune system, leaving them vulnerable to attack, and susceptible to new immunotherapies.

Scientists at the Institute of Cancer Research, London (ICR), found that these “hyper-mutant” tumours rapidly evolve strategies to disguise themselves from the immune system and evade attack. They hope that in the future, the findings could help optimise treatment with immunotherapy, and other drugs such as chemotherapy.

Dr Marco Gerlinger, team Leader in translational oncogenomics at the ICR, said: “Our new study has shown that in highly mutated tumours, cancer and the immune system are engaged in an evolutionary arms race in which they continually find new ways to outflank one another.

Watching hyper-mutated tumours and immune cells co-evolve in such detail has shown that the immune system can keep up with changes in cancer, where current cancer therapies can become resistant – and that we could use immunotherapies to shift the balance of this arms race, extending patients’ lives.

“Next, we plan to study the evolutionary link between hyper-mutant tumours and the immune system as part of a new clinical trial looking at the possible benefit of immunotherapy in bowel cancer.

The study has been published in Nature Communications.

Source: https://www.sciencefocus.com/

Copper-based Nanomaterials Kill Cancer Cells

An interdisciplinary team of scientists from KU Leuven (Belgium), the University of Bremen (Germany), the Leibniz Institute of Materials Engineering (Germany), and the University of Ioannina (Greece) has succeeded in killing tumour cells in mice using nano-sized copper compounds together with immunotherapy. After the therapy, the cancer did not return.

Recent advances in cancer therapy use one’s own immunity to fight the cancer. However, in some cases, immunotherapy has proven unsuccessful. The team of biomedical researchers, physicists, and chemical engineers found that tumours are sensitive to copper oxide nanoparticles – a compound composed of copper and oxygen. Once inside a living organism, these nanoparticles dissolve and become toxic. By creating the nanoparticles using iron oxide, the researchers were able to control this process to eliminate cancer cells, while healthy cells were not affected.

Any material that you create at a nanoscale has slightly different characteristics than its normal-sized counterpart,” explain Professor Stefaan Soenen and Dr Bella B. Manshian from the Department of Imaging and Pathology, who worked together on the study. “If we would ingest metal oxides in large quantities, they can be dangerous, but at a nanoscale and at controlled, safe, concentrations, they can actually be beneficial.

As the researchers expected, the cancer returned after treating with only the nanoparticles. Therefore, they combined the nanoparticles with immunotherapy. “We noticed that the copper compounds not only could kill the tumour cells directly, they also could assist those cells in the immune system that fight foreign substances, like tumours,” says Dr Manshian.

The combination of the nanoparticles and immunotherapy made the tumours disappear entirely and, as a result, works as a vaccine for lung and colon cancer – the two types that were investigated in the study. To confirm their finding, the researchers injected tumour cells back into the mice. These cells were immediately eliminated by the immune system, which was on the lookout for any new, similar, cells invading the body.

Source: https://nieuws.kuleuven.be/

Ultrasound Waves Eliminate Prostate Tumours 2 Times Out Of 3

Blasting prostate cancer with sound waves eliminates tumours in nearly two thirds of patients, a study suggests. Researchers from the University of California at Los Angeles, who tested the technology on 115 men with prostate cancer, saw tumours destroyed in 80 per cent of men they treated.

And 65 per cent of patients were still clear of cancer a year later. Some 47,000 men each year develop prostate cancer in the UK. Despite rapid advances in other cancer types, which have resulted in falling death rates, the number of men who die from prostate cancer is still going up, with 11,800 men in Britain lost each year to the disease. And of those who do survive, many are left with severe side effects as a result of surgery, including incontinence and impotence. The new treatment, called MRI-guided transurethral ultrasound ablation – or TULSA – comes with few of those side effects, the researchers said.  TULSA works by delivering precise doses of sound waves to diseased prostate tissue while sparing surrounding healthy nerve tissue.

It works using on a rod-shaped device, inserted into the urethra, which sends out sound waves from 10 ultrasound-generating elements. The elements are controlled automatically by a software algorithm that can adjust the shape, direction and strength of the therapeutic ultrasound beam. The procedure takes place in an MRI scanner so that doctors can closely monitor treatment and assess the degree and location of heating.

The technique – which uses precise pulses of ultrasound to attack tumours in a session lasting less than an hour – could mean many men avoid surgery

Unlike with other ultrasound systems on the market, you can monitor the ultrasound ablation process in real time and get immediate MRI feedback of the thermal dose and efficacy“, said Research leader Professor Steven Raman. ‘It’s an outpatient procedure with minimal recovery time.’

The treatment, which took an average of 51 minutes, saw prostate volume decreased on average from 39 cubic centimeters 3.8 cubic centimeters a year after treatment. Blood levels of ‘prostate-specific antigen’, or PSA, a marker of prostate cancer, fell by an average of 95 per cent. There were low rates of severe toxicity and no bowel complications.

We saw very good results in the patients, with a dramatic reduction of over 90 per cent in prostate volume and low rates of impotence with almost no incontinence,’ Professor Raman said.

The device, which is already approved for clinical use in Europe, is an advance on another technique that has been used on the NHS for several years called ‘HIFU‘, or high-intensity focused ultrasound. TULSA could also be used to treat men with non-cancerous enlarged prostate – a condition known as benign prostatic hyperplasia or BPH – which affects half of all men over the age of 50, and 60 per cent of those over 60.

There are two very unique things about this system,’ Professor Raman said. ‘First, you can control with much more finesse where you’re going to treat, preserving continence and sexual function. ‘Second, you can do this for both diffuse and localised prostate cancer and benign diseases, including benign hyperplasia.’

TULSA also has the benefit of allowing further treatment if needed, he said. If it fails, then the procedure can be repeated, and more aggressive invasive approaches like surgery and radiotherapy can still be used.

Simon Grieveson, head of research funding at Prostate Cancer UK, said: ‘Over 47,000 men are diagnosed with prostate cancer each year in the UK and many face a difficult decision about what treatment they should have. Current treatments for localised disease, such as surgery or radiotherapy, can be very effective, but they are not without a risk of side effects. ‘In addition, many men with low-risk prostate cancer may be able to avoid radical treatments like this altogether, and instead have their cancer monitored under active surveillance. ‘Whilst novel treatments like this one could potentially cause fewer side effects, we cannot tell from these results alone whether this could be as effective as the treatment options that are currently available and if so, which men could benefit the most.

Source: https://www.dailymail.co.uk/

Cancer’s ‘Internal Wiring’ Predicts Relapse Risk

The “internal wiring” of breast cancer can predict which women are more likely to survive or relapse, say researchers. The study shows that breast cancer is 11 separate diseases that each has a different risk of coming back. The hope is that the findings, in the journal Nature, could identify people needing closer monitoring and reassure others at low risk of recurrence.

Cancer Research UK said that the work was “incredibly encouraging” but was not yet ready for widespread use. The scientists, at the University of Cambridge and Stanford University, looked in incredible detail at nearly 2,000 women’s breast cancers. They went far beyond considering all breast cancers as a single disease and beyond modern medicine’s way of classifying the tumours.

Doctors currently classify breast cancers based on whether they respond to the hormone oestrogen or targeted therapies like Herceptin. The research team analysed the genetic mutations inside the tumour to create a new way of classifying them.

By following women for 20 years, they are now able to show which types of breast cancer are more likely to come back.  “This is really biology-driven, it’s the molecular wiring of your tumour, said Prof Carlos Caldas. Once and for all we need to stop talking about breast cancer as one disease, it’s a constellation of 11 diseases. “This is a very significant step to more precision-type medicine.”

Source: https://www.bbc.com/

‘Epigenetic’ Gene Tweaks Could Trigger Cancer

You could be forgiven for thinking of cancer as a genetic disease. Sure, we know it can be triggered by things you do – smoking being the classic example – but most of us probably assume that we get cancer because of a genetic mutation – a glitch in our DNA. It turns out that this is not quite the end of the story.

We now have the first direct evidence that switching off certain genes – something that can be caused by our lifestyle or the environment we live in – can trigger tumours, without mutating the DNA itself. The good news is that these changes are, in theory, reversible.

All cells contain the same DNA, but individual genes in any cell can be switched on or off by the addition or subtraction of a methyl group – a process known as epigenetic methylation.

For years, researchers have known that mutations to our DNA – either those passed on at birth or those acquired as a result of exposure to radiation, for example – can cause cancer. But epigenetic changes have also been implicated in cancer because abnormal patterns of gene methylation are seen in virtually all types of human tumours.

For example, a gene called MLH1 produces a protein that repairs DNA damage. It is often mutated in colon cancer tumours, but in some tumour samples the gene is healthy, but appears to have been silenced by methylationThe problem is that it has been difficult to test whether abnormal methylation occurs as a result of a tumour or is a cause of its growth.

In genetics you can easily delete a gene and see what the consequence is, but it’s much harder to direct methylation to specific regions of the genome,” says Lanlan Shen of Baylor College of Medicine in Houston, Texas.

To get round this problem, Shen and her colleagues used a naturally occurring sequence of DNA, which draws in methyl groups to methylate nearby genes. They call it their “methylation magnet”.

The team inserted this sequence next to the tumour suppressor gene, p16, in mouse embryonic stem cells. These embryos then developed into mice that carry the “methylation magnet” in all of their cells. The team focused on methylating p16 because it is abnormally methylated in numerous cancers.

They monitored the rodents for 18 months – until they reached the mouse equivalent of middle age. Over this time, 30 per cent of the mice developed tumours around their body, including in their liver, colon, lungs and spleen. None of a control group of genetically identical mice developed tumours.

Some tissues showed faster methylation than others, for example in the liver, colon and spleen, and that’s exactly where we saw the tumours grow,” says Shen. “It seems like methylation predisposed the tissue to tumour development.” She reckons that methylation silences p16, which lifts the break that it normally places on any abnormal cell division.

Source: https://www.newscientist.com/