UK Innovators target nanoparticles at inoperable cancers

Author: from Medicines Discovery Catapult

At a point of critical clinical need for improved treatments for pancreatic and head and neck cancers, a partnership of healthcare innovators set out to revolutionise radiotherapy for inoperable, and the most difficult to treat tumours.

With the aim of achieving a higher quality of life for those with unfavourable prognoses, this project, funded by Innovate UK, the UK’s innovation agency, brings together partners with a wealth of experience and specialist know-how in the areas of nanoparticle development, drug delivery and bioimaging.

The pioneering work being conducted will target cancerous cells more selectively, enabling a reduced dose of radiation, which would lower the toxic effects a patient receives as a result.

This targeted approach will employ Xerion Healthcare’s non-toxic radiosensitiser – this heightens the cells’ sensitivity to radiotherapy, increasing the likelihood of successful treatment while reducing the often devastating side effects.

To ensure the nanoparticles carrying the therapeutic agent reaches deep inside the tumour, Active Needle Technology’s unique delivery system conveys the treatment to the cancerous cells with the assistance of ultrasonic vibrations, which not only allow accurate placement, but also enables an optimal distribution throughout the tumour and limits damage of healthy cells in the process.

Medicines Discovery Catapult’s (MDC) advanced pre-clinical imaging suite and state-of-the-art expertise in complex medicines validation will undertake in-life imaging of the nanoparticle distribution, allowing the partners to validate its biodistribution in tumour and across other tissues and organs.

Ian Quirk, CEO of Active Needle Technology said:

“For patients suffering from a range of late stage cancers, treatment options can be limited. The effectivity and accuracy of Active Needles delivery of Xerion Healthcare’s ground-breaking new anti-cancer treatment is poised to revolutionise radiotherapy, and offer the hope of recovery for vast numbers of patients. We’re delighted to be working with Medicines Discovery Catapult to take the technology one step closer to the clinic.”

Dr Gareth Wakefield, Chief Technology Officer from Xerion Healthcare said:

“Effective direct tumoural delivery of anti-cancer agents is a key stepping stone to getting our nanoparticle products into clinical trials and into treatment programs for patients with inoperable tumours. Partnering with Active Needles unique ultrasonic delivery system and MDC’s real time imaging allows us to optimise the delivery system for maximum efficacy.

“Late presenting inoperable tumours require very high dose radiotherapy for successful treatment. This can often have very severe side effects or simply not be possible due to nearby sensitive organs. This project gives us a way to boost the effectiveness of the treatment without increasing the whole body dose.”

Professor Peter Simpson, Chief Scientific Officer at Medicines Discovery Catapult (MDC) said:

“MDC is pleased to be providing our state of the art imaging facilities and complex medicines expertise in this exciting collaboration with Active Needle Technology and Xerion Healthcare – to assess the biodistribution and efficacy of this nanoparticle approach.

“Complex medicines have the potential to address patients’ problems which conventionally administered small molecules and monoclonal antibodies cannot. This project is a very encouraging example of exploring how using an advanced drug delivery technology could improve drug biodistribution, and so improve the targeting and efficacy of potentially toxic therapeutics.”

Although great progress has been made in the treatment of some common cancers, there remain many indications where there has been little improvement in care over decades. Pancreatic cancer is on course to become the second leading cause of cancer mortality by 2030 with head and neck cancer currently seeing a 50% mortality rate. It has never been more timely or pertinent for research in this space to be undertaken.

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2020-12-19T08:18:56-07:00December, 2020|Oral Cancer News|

Addenbrooke’s to use Microsoft’s AI tool to speed up cancer treatment

Author: staff

Microsoft said that Addenbrooke’s Hospital in Cambridge, UK, will use its artificial intelligence (AI) technology powered InnerEye tool for speeding up cancer treatment.

Developed at its Cambridge Research Lab, the InnerEye project helps in developing AI models that leverage the hospital’s own data to automatically show tumours and healthy organs on patient scans. These are then checked and confirmed by a clinical oncologist prior to giving treatment to the patient, said Microsoft.

According to the tech major, the process will reduce the otherwise lengthy treatment planning stage, which is crucial for head and neck cancers, which can multiply quickly if left untreated. Microsoft claims that InnerEye can help execute contouring process in complex cases 13 times faster than the current approach.

Addenbrooke’s Hospital oncologist and InnerEye co-lead Dr Raj Jena said: “The results from InnerEye are a game-changer. To be diagnosed with a tumour of any kind is an incredibly traumatic experience for patients.

“So as clinicians we want to start radiotherapy promptly to improve survival rates and reduce anxiety. Using machine learning tools can save time for busy clinicians and help get our patients into treatment as quickly as possible.”

Run by Cambridge University Hospitals NHS Foundation Trust, Addenbrooke’s is a teaching hospital, research centre, and also a designated academic health science centre.

Addenbrooke’s Hospital and Microsoft are said to have been collaborating over the last eight years to develop and pilot InnerEye. The hospital will become the first NHS facility to have introduced a deep-learning solution trained on its own data, once the AI tool is deployed.

Microsoft said that to make sure that all hospitals can use the InnerEye Deep Learning Toolkit, the company has made it available freely as opensource software. However, clinical use of machine learning models is subject to approval from relevant regulators.

Microsoft Research Cambridge principal research manager Javier Alvarez-Valle said: “AI models trained with InnerEye are changing the way cancer is treated, speeding up the process to give patients greater peace of mind and empowering clinical oncologists with an AI assistant.

“The AI works in the background, so clinical oncologists just open up the scans on their computer and they can see what their AI model has highlighted. The clinical oncologist then decides what to do with that information.

“AI models trained with InnerEye will be hosted in Microsoft’s Azure cloud, so all the data is securely held in the UK and only available to the medical staff who need to use it.”

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2020-12-12T10:01:59-07:00December, 2020|Oral Cancer News|

First patient participates in immunotherapy trial despite COVID-19 pandemic

Author: UC-San Diego, Reviewed by Emily Henderson, B.Sc

Since 2016, Bernard Thurman has undergone traditional treatments, experimental therapies and surgeries to counter the cancer within him, but nothing has successfully eradicated the disease. Earlier this year, the oncologists in Los Angeles who were treating him referred Thurman to a personalized cancer therapy trial being developed at Moores Cancer Center at UC San Diego Health.

“Truly, I am running out of options, as far as treatment goes,” said Thurman, whose cancer developed in his tonsils and has since spread to his lungs.

“The latest immunotherapies, both the FDA-approved and the experimental, were proving ineffective. Obviously, it was time to go in a different direction.”

Thurman met with Ezra Cohen, MD, associate director for translational science at Moores Cancer Center, in mid-March to discuss an investigational cell therapy that uses a patient’s own immune cells — specifically tumor infiltrating lymphocytes (TIL) — to seek and destroy their own unique cancer cells.

Days after this meeting, COVID-19 swept the country, forcing hospitals to rethink which procedures could continue and which would need to be paused. Because the TIL trial requires that patients be hospitalized, it was put on hold. Thurman was disappointed.

“Don’t let the pandemic make you decide to put off cancer treatment,” said Thurman. “You may or may not get COVID, but cancer will kill you if you don’t treat it. So, don’t delay it.”

Knowing the urgency of treatment, Cohen, a head and neck oncologist, suggested an alternative trial.

“We treated Mr. Thurman on an initial clinical trial with a different type of immunotherapy, an antibody, and he did fairly well at the beginning,” said Cohen. “But, again his cancer began to grow and, unfortunately, progressed.”

While the COVID-19 pandemic continues to sicken people worldwide, UC San Diego Health has resumed previously paused medical services. This allowed Cohen, and colleagues Gregory Daniels, MD, PhD, and Aaron Miller, MD, PhD, to reinitiate the Phase I TIL trial.

After seeing that Thurman’s cancer was unabated on the immunotherapy trial, he was enrolled as the first patient and received a personalized TIL therapy on Tuesday.

“Treating our first patient with his own cells generated at UC San Diego marks a milestone following years of preparation leveraging the core strengths of the cancer center — patient care, research and collaboration,” said Daniels, an oncologist specializing in skin and head and neck cancers and protocol principal investigator for the TIL trial.

TIL therapy has been around for decades, with some success in treating melanoma — the most serious form of skin cancer.

Together, UC San Diego and La Jolla Institute for Immunology (LJI) researchers are taking TIL therapy a step further by selecting the T-cells that are most likely to be responsive against an individual’s cancer. They are also expanding the therapy to treat melanoma and head and neck cancers.

“Cell therapy has been proven effective for a number of different patients, but we want to improve upon it,” said Miller, a medical oncologist. “We want to make it more effective, less toxic and more applicable to a broader population of cancer patients.”

Engineering Thurman’s TIL therapy involved a weeks-long, personalized process that began with Thurman undergoing a tumor biopsy at Jacobs Medical Center at UC San Diego Health in October.

Tissues samples were then sent to LJI where a team led by Stephen Schoenberger, PhD, and Bjoern Peters, PhD, developed a novel technology platform to identify mutations recognized by the patient’s own immune system. Early funding support from the Immunotherapy Foundation created the infrastructure to develop the process, which was first used to develop a personalized cancer vaccine trial in 2018.

An algorithm is used to isolate tumor-infiltrating lymphocytes, a type of T-cell, with the strongest response against Thurman’s cancer mutations.

“We are taking the patient’s tumor, sequencing the protein coding portion of the genome, finding out which mutations can be recognized by the patient’s immune system, and then looking for the TIL fragments that contain those T-cells,” said Schoenberger, an adjunct professor of medicine at UC San Diego School of Medicine. “If we can identify which TIL can recognize the mutations that are selectively expressed in the tumor, selectively grow those and reinfuse them to the patient, we will hopefully have a more potent and more effective therapy. That’s our advance.”

Once the T-cells that appeared to be initiating the strongest immune system response to Thurman’s cancer are identified, a team led by Dan Kaufman, MD, PhD, at the Advanced Cell Therapy Laboratory at UC San Diego multiply the specified T-cells by the billions.

The cells are autologous: They are the patient’s own cells, simply lab-grown.

At Jacobs Medical Center, Thurman underwent an infusion of these engineered cells and a high-dose interleukin-2, a biologic therapy used to boost T-cell response in cancer therapy. Ideally, within weeks, the TIL therapy will shrink tumors.

“All of us involved in this research project want one thing, and one thing only, and that is for patients to get better and to offer new effective therapies to patients with cancer,” said Schoenberger.

Thurman wants that too. He is optimistic, but also understands that he is the first patient to receive this experimental, personalized cancer therapy. He thinks others should enroll in clinical trials too.

“Clinical trials are a lifeline. Give it a shot. You may literally have nothing to lose,” said Thurman. “It may be beneficial, personally. It may not. But it will further research for other patients down the road and hopefully help others in the future.”

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2020-12-12T09:56:17-07:00December, 2020|Oral Cancer News|

Deep learning models for image-guided RT in head and neck and prostate cancers

Author: Lisa Kuhns

Machine learning models achieve clinically acceptable accuracy in image segmentation tasks in radiotherapy planning and reduce overall contouring time for head and neck and prostate cancers, according to a recent study in JAMA Network Open (2020;3[11]:e2027426. doi:10.1001/jamanetworkopen.2020.27426)

Personalized radiotherapy planning requires large time commitments for oncologists and processes often vary among experts and institutions.

Authors aimed to explore clinically acceptable autocontouring solutions that can be integrated into clinical practice and used in different radiotherapy areas.

Researchers evaluated multicenter imaging data set made up of 519 pelvic and 242 head and neck computer tomography scans from 8 clinical sites. Patients in the study were diagnosed with either prostate or head and neck cancer. The models were trained to automatically delineate organs at risk and evaluated internal and external datasets. Models were compared against expert annotations in an interobserver variability (IOV) study.

For 13 of the 15 structures, the models performed within the bounds of expert IOV. For internal vs external data sets, the models achieved mean [SD] Dice scores for left femur at 98.52% and 98.04% (P = .04), respectively.

“In this study, the models achieved levels of clinical accuracy within expert IOV while reducing manual contouring time and performing consistently well across previously unseen heterogeneous data sets,” concluded the study authors. “With the availability of open-source libraries and reliable performance, this creates significant opportunities for the transformation of radiation treatment planning.”—Lisa Kuhns

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2020-12-11T09:20:35-07:00December, 2020|Oral Cancer News|

Personalized vaccines: the new frontier in cancer treatment

Author: Udbhav Venkataraman

Exciting results from a new clinical study showed that a personalized vaccine combined with an immunotherapy drug had a promising response rate in patients with advanced incurable head and neck cancer.

Dr. Julie Bauman, chief of Hematology and Oncology at the University of Arizona College of Medicine — Tucson, led a phase one clinical trial with the pharmaceutical company, Moderna, to test the combined use of personalized vaccines created from tumor DNA with the immunotherapy drug pembrolizumab.

Of the 10 patients involved in the study, five of the them responded to the treatment, meaning 30% of the cancer mass had decreased. Furthermore, two of the patients completely responded, meaning that cancer could not be detected.

Molly Cassidy is one of those two patients. What was initially determined to be a stress-related ear-ache turned out to be an aggressive case of squamous cell carcinoma, a form of head and neck cancer.

Head and neck cancers impact the linings of the mouth and throat. Risk factors for this disease include alcohol consumption, smoking and other environmental carcinogens that we are all exposed to. It can also be caused by human papillomavirus (HPV).

Cassidy did not fit this profile at all.

“I’m HPV-negative. I didn’t drink. I didn’t smoke. I’m a woman. I was the first person in my family to have cancer. I was 35 when I got my diagnosis,” Cassidy said. “I was also in really good health … To hear that I had cancer was really surprising.”

With an initial prognosis that the cancer was curable, Cassidy underwent a standard but invasive surgery followed by a grueling series of radiation and chemotherapy sessions over the next few months.

Just a week after completing Cassidy’s initial treatment plan, the cancer returned aggressively. She had several tumors in her neck and they were spreading to her lungs. Her prognosis became bleaker.

“Having such a quick recurrence was not a good sign … they put me on a palliative plan and I was told I need to get my affairs in order,” Cassidy said. “I wasn’t expected to live for more than a year.”

Cassidy now had advanced incurable head and neck cancer which occurs when an initial cancer treatment fails and the cancer returns. This combined with the fact that she was HPV negative made her eligible for Bauman’s clinical study.

One of the recent frontiers of cancer research has been immunotherapy — harnessing our immune systems to fight cancer. Our immune system is able to detect and attack foreign invaders in our bodies, including cancer cells. However, these cells develop ways to hide from the immune system.

Immunotherapy can involve using medication to activate and train the immune system to recognize and eliminate these cancer cells. When this treatment is effective, the response can be long-lived.

“I can give you chemo and drive you to a complete response, but as soon as chemo is not there, the cells that are left become resistant and grow back,” Bauman said. “Immunotherapy leaves behind an army of T-cells that if the cancer rears its ugly head again, will presumably kill it.”

According to Bauman, the current U.S. Food and Drug Administration-approved therapies are non-specific. These therapies generally activate the T-cells of the immune system which recognize foreign invaders. This method means that T-cells that recognize cancer cells would be activated. This method of therapy however has a low effectiveness rate.

“In head and neck cancer, this class of therapy is successful 10-15%of the time … We want that to be more often,” Bauman added.

Furthermore, there can be auto-immune side effects because T-cells that recognize our own healthy tissues may start attacking those very tissues.

This is where new and fascinating technology comes into the picture: personalized vaccines. This approach is a specific approach, where T-cells are activated based on the mutations of the patient’s cancer.

After taking a sample of cancer cells from the patient, those cells’ DNA is sequenced. Using a computational algorithm, the cancer DNA is compared to the patient’s healthy DNA to find the specific mutations present in that patient’s cancer. From all those mutations, Moderna is able to synthesize a messenger RNA vaccine, which can be used to train the appropriate T-cells to recognize abnormal proteins from these cancer cells.

A helpful video about the process can be found at the UA Health Sciences website. The clinical trial consisted of using both this personalized vaccine approach with the FDA approved T-cell activator pembrolizumab.

“The trial is the combination of using those mutations almost like a trojan horse … educating the immune system to see those mutated proteins at the same time as we give the unbridled T-cell activator,” Bauman said. “We’re awakening T-cells, but we’re saying this is the particular class of T-cells that we are calling.”

For the trial, each patient was given two doses of pembrolizumab over six weeks. During this time, the vaccine was developed by Moderna. After the vaccines were created, the patients received one dose of their vaccine every three weeks for nine weeks along with the pembrolizumab, and the cancer was monitored using a CAT scan.

And the results show that the vaccines are safe. This seems really promising and exciting to pursue.

“Although it is only 10 patients, and we have to not only overpromise … it is a really strong signal to expand the study and to see if we continue to see what we saw with these 10 patients,” Bauman said.

“When I was going into treatment, I was really ill and the treatments themselves were pretty hard on me. Cancer treatment is no walk in the park,” Cassidy said. “But once I got through the treatment’s initial side effects, I started to notice an increase in my energy and I wasn’t in as much pain.”

Having completely responded to her treatment, Cassidy is now able to live a normal life. She has spoken with various dentists and used her platform to help educate people about the prevalence and signs of oral cancers and the importance of understanding what the inside of our mouths are supposed to look like.

“It also brought forth what are the most important things for me — my son and husband and the importance of slowing down and enjoying my time with my family,” Cassidy said.

There are many new things that Bauman is looking into researching further. As they expand the trial to 40 participants for the next phase of trials, she is exploring how to optimize the vaccine.

“If we can selectively educate the immune system … we can have a therapy that is active, could drive a permanent response and not be toxic or harsh on the rest of the body,” Bauman said.

Bauman also mentioned that this optimization might mean potentially experimenting with a different drug than pembrolizumab for treatment, although this is a great start. They have also taken samples of the T-cells from the patients to see which types of mutations the T-cells respond best to.

“People who have advanced in cancer … have extraordinary suffering because cancer is uncontrolled in this area where things are critical to our humanity, like talking and breathing and eating and kissing and smiling. To be able to reverse that suffering and offer that hope is uniquely gratifying,” Bauman said.

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2020-12-09T06:51:37-07:00December, 2020|Oral Cancer News|

NHS to trial blood test that detects over 50 early-stage cancers

Author: Sara Rigby, PA Science

A blood test that may be able to spot more than 50 types of cancer will be piloted by the NHS, chief executive Sir Simon Stevens has announced. Developed by US-based company Grail, the test checks for molecular changes.

The Galleri blood test, which can detect early stage cancers through a simple blood test, will be piloted with 165,000 patients in a deal struck by NHS England.

NHS England said research on patients with signs of cancer suggests the test can identify many types that are difficult to diagnose early, such as head and neck, ovarian, pancreatic, oesophageal and some blood cancers.

If the programme shows that the test also works as expected for people without symptoms, it will be rolled out to become routinely available. The test could help meet the NHS goal of increasing the proportion of cancers caught early, which can be the key to reducing cancer mortality.

Patients who have their condition diagnosed at stage one – when the tumour is small and hasn’t spread – typically have between 5 and 10 times the chance of surviving compared with those found at stage four – when it has spread to at least one other organ.

“While the good news is that cancer survival is now at a record high, over a thousand people every day are newly diagnosed with cancer,” said Stevens. “Early detection – particularly for hard-to-treat conditions like ovarian and pancreatic cancer – has the potential to save many lives. This promising blood test could therefore be a game-changer in cancer care, helping thousands more people to get successful treatment.”

The pilot, which is due to start in mid-2021, will involve 165,000 people. This will include 140,000 participants aged 50 to 79 who have no symptoms but will have annual blood tests for three years. Another 25,000 people with possible cancer symptoms will also be offered testing to speed up their diagnosis after being referred to hospital in the normal way.

People will be identified through NHS records and approached to take part. Anyone with a positive test will be referred to the NHS for investigation.

Results of these studies are expected by 2023, and if outcomes are positive, then they would be expanded to involve around one million participants across 2024 and 2025.

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2020-11-29T15:12:54-07:00November, 2020|Oral Cancer News|

Thousands of Brits may be living with mouth cancer after ‘healthy’ dad dies aged 37

Author: Alan Weston & Sam Truelove

A dentist has warned that thousands of Brits may be unknowingly living with mouth cancer after a “healthy” dad-of-seven died from the disease.

Alan Birch, 37, lived a healthy, active lifestyle and did not drink or smoke but died from an aggressive form of mouth cancer in April. The self-employed plasterer, from Wirral in Merseyside, was diagnosed with mouth cancer in 2018, and had to have 90 per cent of his tongue removed, Liverpool Echo reports.

Despite Alan undergoing both radiotherapy and chemotherapy, the cancer returned each time and specialists told his devastated family there was nothing more they could do for him.

Alan and his partner of 12 years, Debbie McDonough, decided to get married in February, but he tragically died a few weeks later in April.

With the latest figures from the British Dental Association showing that 19 million treatments have been missed due to lockdown, dentists are now concerned about the number of cases of mouth cancer that will have potentially gone undiagnosed this year as a result.

Mouth cancer takes more lives than cervical cancer and testicular cancer combined, with 8,722 new cases reported in the UK last year. This is a 58 per cent increase compared to a decade ago and a 97 per cent rise since 2000.

Debbie said: “I would urge people to always keep on top of their dentist appointments as they are the ones who notice the warning signs for mouth and tongue cancer.

“Always be careful of ulcers especially if you have them longer than two weeks, and never think you are wasting an appointment if you are worried about anything. It’s better to be safe than sorry.”

New research revealed that 52 per cent of people living in the North-West are unaware their dentist will screen them for mouth cancer during a routine check-up.

Dr Catherine Tannahill, dentist and director of clinical dentistry at Portman Dental Care, which carried out the research, said: “As dentists we see first-hand the impact this disease can have, and that’s why we want to ensure people are aware of what the signs and symptoms are, what to do if they spot an issue and what steps they can take to reduce the risk of developing mouth cancer.

“This is now more important than ever before, as thousands of diagnoses may have potentially been missed this year due to dental practices having to close in initial lockdown, and the subsequent backlog of appointments since.

“While this may sound alarming, early diagnosis of mouth cancer leads to a 90 per cent survival rate, which is why it is imperative that people continue visiting their dentist for regular check-ups.

“Dentists play a pivotal role in the detection of mouth cancer, as they will always check for the classic signs of the disease during any routine appointment. As a dental professional, it was concerning to see through our research how many people were unaware of this.”

According to Dr Tannahill, the most common signs of mouth cancer are mouth ulcers that do not heal in three weeks, unusual lumps or swelling in the mouth, head or neck, and red and white patches within the mouth.

Mouth cancer can appear in the tonsils, the roof or floor of the mouth and in the tongue, and people should regularly check all areas of their mouth.

“There are also a few simple lifestyle changes that people can make that can help reduce the risk of developing mouth cancer,” Dr Tannahill added.

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2020-11-29T15:06:57-07:00November, 2020|Oral Cancer News|

Why immunotherapy only works for some with head and neck cancer

Author: Katie Pence, University of Cincinnati

Image of a healthy T cell on left compared to a cancer T cell on right. Credit: Ameet Chimote

University of Cincinnati researchers have discovered new clues into why some people with head and neck cancer respond to immunotherapy, while others don’t.

Findings published in the Journal for ImmunoTherapy of Cancer show that it could all come down to “channeling” the power and function within one particular type of immune cell.

Laura Conforti, Ph.D., professor in the Department of Internal Medicine at the UC College of Medicine and corresponding author on the study, says understanding these mechanisms could help in creating combination treatments to more effectively treat some patients with cancer.

She points out that head and neck cancers are the sixth most common cancers in the world, affecting about 53,000 Americans every year. To combat the deadly disease, doctors often turn to immunotherapy, which boosts the body’s own immune system in an effort to identify and kill cancer cells.

“Our immune cells are naturally programmed to distinguish between our body’s ‘normal’ cells and what they see as ‘foreign’ cells and attack only the foreign cells,” explains Conforti.

She says the immune cells—called T cells— lead the body’s attack against cancers but the impact of that attack can be proven futile if a molecule in cancer cells is able to bind to an immune checkpoint in the T cells and effectively “turn them off like a light switch.” As a result, the T cells leave the cancer cells alone, which Conforti says is “a major problem,” especially for head and neck cancers.

A known immunotherapy treatment (pembrolizumab) targets the checkpoint molecule and blocks the “off switch” of the T cells, but scientists are trying to determine why this method works in some people and not in others. Conforti further explains that the ability of these T cells to attack and destroy cancer cells relies on molecules called potassium ion channels, which are present in T cells and are responsible for a variety of functions, including killing cancer cells.

Conforti’s team includes co-lead authors Hannah Newton, Ph.D., a recent UC doctoral graduate; Vaibhavkumar Gawali, Ph.D., postdoctoral fellow; and Ameet Chimote, Ph.D., research scientist in Conforti’s lab. The team found that when patients with head and neck cancer were given immunotherapy at UC Medical Center, T cells in these patients showed increased activity in these channels, allowing them to more effectively reach the cancer cells and kill them.

The team also found that after the treatment was delivered to patients, these channels in the T cells circulating in their blood were more active, meaning they were more equipped to continue fighting off the cancerous cells.

“We also saw that head and neck cancer patients who were responding to this immunotherapy, meaning their tumors were shrinking, had greater channel activity in their T cells soon after treatment, and the T cells had more ability to enter into the tumors to continue killing cancer cells,” Conforti adds. “However, patients who did not respond lacked this increased activity.

“Immunotherapy is not one-size-fits all, since some patients respond to immunotherapy, while others don’t, but our research shows that ion channels within T cells of these patients play a crucial role in the response of immunotherapy. Now that we know the benefits of these channels, more research is needed to look at ways we can activate them or create combination therapies to help patients increase their chance of survival.”

Team member Newton, who recently completed her doctorate at UC and is now working at the National Institutes of Health-sponsored Frederick National Laboratory for Cancer Research, says that working on this study at UC was invaluable.

“This research allowed me to collaborate with diverse professional individuals including medical oncologists, clinical coordinators and other researchers and gave me the opportunity to better understand the bench-to-bedside procedure for drug development,” Newton says. “Most importantly, it could help clinicians determine more personalized and effective treatment combinations for patients with head and neck cancer.”

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2020-11-25T13:38:19-07:00November, 2020|Oral Cancer News|

UArizona clinical trail expanding after early results with personalized cancer vaccine

Author: Karly Tinsley

Despite the pandemic, groundbreaking research has not stopped at the University of Arizona. Researchers with the UArizona Health Sciences are working to help treat cancer by using personalized vaccines. It works in combination with the immuno-therapy drug Pembrolizumab.

According to the UArizona, Julie E. Bauman, MD, MPH, deputy director of the University of Arizona Cancer Center and a professor of medicine and chief of the Division of Hematology and Oncology at the UArizona College of Medicine – Tucson, presented preliminary data on the first 10 patients with head and neck cancer, seven of which were treated at Banner – University Medicine, the clinical partner for the UArizona Cancer Center. Five of the 10 patients experienced a clinical response to the personalized cancer vaccine, and two patients had a complete response after the treatment (no detectable disease present).

Molly Cassidy is one of the 10 who went through the trial.

“I was a young healthy woman, so it was a big shock to get diagnosed,” said Cassidy.

She was first diagnosed with oral cancer after complaining of an ear ache. Dentists initially found a tumor in her tongue that was later identified as cancer. She then went through treatment for the tumor, but her cancer came back aggressively.

“I had tumors throughout my neck, in my lungs, I was really really ill,” said Cassidy.

At this time she was seeing Dr. Bauman, who said they both understood her chances of survival were slim at that point.

“I was writing my will,” said Cassidy.

“She asked me to prepare her. It was not viewed as curable and she began to do end of life work,” said Dr. Bauman.

That’s when Dr. Bauman offered her the option of joining her clinical trial. It’s a treatment tailored specifically to the patient. Their cancer cells are used to develop a personalized vaccine that teaches their immune system how to recognize and destroy their cancer.

According to UArizona, to identify the patient-specific mutations of the cancer, mutated DNA from the patient’s tumor is simultaneously sequenced with healthy DNA from the patient’s blood. Computers compare the two DNA samples to identify the unique cancer mutations.

The results are used to develop a set of genetic instructions that are loaded onto a single molecule of messenger RNA (mRNA) and made into a vaccine. These instructions teach immune cells such as T-cells – white blood cells that help protect against infection – how to identify and attack the mutated cancer cells.

“It’s a medicine that is individualized, personalized, and is not one size fits all,” said Dr. Bauman.

Cassidy began the series of 9 shots of her specific vaccine and for the first time things were improving.

“We were cautiously hopeful,” said Dr. Bauman.

It makes her one of two patients in the trial who’ve responded completely, with cancer no longer detectable on a CT scan.

“To see that reversed was striking, stunning, extremely unusual,” said Dr. Bauman.

The trial is now being expanded to more patients due to the early results, as Dr. Bauman is now working with 40 patients with head and neck cancer. Giving those like Cassidy a second chance to picture life after a cancer diagnosis.

“To have such a great response has given me so much of my life back,” said Cassidy.

Her treatment is for two years in the trial, and so far Cassidy remains in complete response.

Dr. Bauman said a personalized vaccine also strives to be less toxic on the body, by not awakening cells that typically attack the organs with regular immunotherapy.

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2020-11-21T10:33:28-07:00November, 2020|Oral Cancer News|

Deciphering molecular intelligence for early oral cancer detection

Author: Muy-Teck Teh, Senior Lecturer, Queen Mary University of London

Muy-Teck Teh, Senior Lecturer from Barts and the London School of Medicine & Dentistry, Queen Mary University of London discusses how a novel low-cost rapid digital diagnostic test could help save lives and reduce head and neck cancer burden worldwide:

Head and neck squamous cell carcinoma (HNSCC) is a heterogenous group of diseases involving malignancies of the oral cavity, pharynx, larynx, nasal cavity, paranasal sinuses and salivary glands.

It is the sixth most common cancer, with an incidence of around 600,000 cases worldwide. These numbers are expected to double by 2035, according to the World Health Organization (WHO).

Despite advances in treatment options for oral cancer (mostly oral squamous cell carcinoma, OSCC), the 5-year survival rate (~50%) has not improved over the last half century, mainly because many malignancies are not diagnosed until late stages of the disease.

Published data showed that over 70% of OSCC patients have some form of pre-existing oral premalignant disorder (OPMD) lesions amenable to early diagnosis and risk stratification. Hence, the potential to reduce the morbidity and mortality of OSCC through early detection is of critical importance.

Century old diagnostic method needs upgrading
OPMDs are very common but clinicians are unable to differentiate between high- and low-risk OPMDs through histopathological gold standard method based on subjective opinion provided by pathologists.

As there is currently no quantitative method to detect high-risk lesions, most OPMD patients are indiscriminately put on time consuming, costly and stressful surveillance. Such “waiting game” creates unnecessary stress and anxiety in majority of low risk patients (88%), whilst delaying and under-treating minority of high-risk patients (12%).

Current requirements of biopsy for histopathology are quite strict and the insensitive nature of histopathology means that biopsies need to be quite large (5-10mm) so that pathologists could see differences between the lesion and its margin. Hence, the scalpel biopsy procedure will need suturing and causes significant pain and stress to the patients. An experienced pathologist may be better at spotting cancerous cells compared to an inexperienced pathologist to provide a subjective opinion based on his/her visual findings. The whole process takes at least 1 week. Patients may seek second opinions from different pathologists, further delaying treatments.

Most importantly, histopathology is currently NOT able to definitively differentiate between low and high-risk lesions.

Early cancer detection saves lives and costs
A systematic review on OPMD estimated a malignancy conversion rate of 12%, but cancer detection rates have been reported to be lower (7%) despite patients being referred using the fast-track, two-week suspected cancer referral system in the UK.

A 10-year audit (2002-2012) in a district general hospital in the UK found a dramatic 450% increase in the annual number of patients referred using the two-week cancer referral pathway but cancer detection rate decreased by 50% indicating that a large proportion of referred cases were false positives thereby unnecessarily increasing the burden on secondary care.

The latest National Head and Neck Cancer Audit 2014 in the UK found that over 70% of patients waited between 10-21 days from biopsy to histopathology reporting. Delayed treatment directly causes poor long-term morbidity and survival.

Cost-effectiveness studies (UK and Taiwan) have independently demonstrated significant cost savings when OSCC patients were treated at stage 0 (premalignant) or stage 1 compared to stage 2-4. Collectively, these evidenced a significant disease and financial burden to the current healthcare systems.

It has been repeatedly emphasised that early diagnosis of OSCC is the key to improving patient outcome. Hence, a rapid effective diagnostic method that can identify early cases of high-risk OPMD patients would help alleviate the current disease and financial burdens in treating OSCC patients.

A novel intervention: The qMIDS digital cancer technology
All cellular processes are tightly regulated by a complex network of interacting biomolecules. Given that mRNA transcription precedes protein translation, change in gene expression levels often precedes visible pathological manifestation. Hence, changes in gene expression serve as key signals for subsequent disease initiation and manifestation.

Dr. Teh has pioneered a molecular test qMIDS (quantitative Malignancy Index Diagnostic System)1, that deciphers key molecular biomarkers into quantitative diagnostic results for clinicians to identify high-risk oral lesions within 90 mins (Figure 1). The qMIDS assay involves using qPCR to measure a panel of 16 biomarkers associated with a key oncogene FOXM12-7, implicated in the regulation of the cell cycle, genomic stability, chromatin maintenance, stem cell regulation, matrix and immune modulation.

FOXM1 transcription factor has been shown to be amongst the top upregulated oncogenes across 39 cancer types and is a major predictor of poor cancer prognosis2-7. The qMIDS assay represents the first ever FOXM1-based cancer diagnostic test and it has been validated on over 450 participants from UK, Norway, China, Pakistan and India, demonstrating a rapid minimally invasive method enabling precise digital quantitative cancer risk stratification in otherwise ambiguous dysplastic lesions1, 8.

Their previous collaborative studies provided independent evidence that the pathophysiology of OSCC was molecularly indistinguishable between the Asian and European specimens. The qMIDS test robustly quantifies a universal FOXM1-driven oncogenic program in OSCC which transcends ethnicity, age, gender and geographic origins1, 8. The qMIDS diagnostic efficiency was found to have; Sensitivity: 88%; Specificity: 96%; Accuracy: 92%; False positive rate: 4.5%; False negative rate: 12%; Area under the curve: 0.945.

qMIDS requires only a tiny amount of tissue biopsy (1 mm) compared to conventional surgical biopsy (>5-10 mm) which are highly invasive and may require general anaesthesia for patients unable to tolerate injections of local anaesthesia. The minimally invasive qMIDS also reduces the overall time from biopsy to results (<1.5 hours with qMIDS compared with >1 week for histopathology). A simple and small 1 mm punch biopsy requires significantly less time to perform than a scalpel biopsy. The small sample requirement also enables multiple punch biopsies sampling for patients with large oral field changes.

Although invasive, using tissue biopsy provides a more accurate and reliable diagnosis compared to non-invasive (visual imaging scopes/stains, saliva or cytology) methods which are not reliable and still ultimately require tissue biopsy for confirmation by pathologists.

In conclusion, a minimal invasive affordable molecular test such as qMIDS could be used for rapid risk stratification of OPMDs to enable early detection and treatment of high-risk patients. Primary prevention through early detection of cancer offers the best chance for improving patient survival and reducing overall costs and HNSCC cancer burden especially in developing countries where the disease is most prevalent.

Further details of qMIDS could be found here:

1 Teh MT, Hutchison IL, Costea DE, et al. Exploiting FOXM1-orchestrated molecular network for early squamous cell carcinoma diagnosis and prognosis. Int J Cancer. May 1 2013;132(9):2095-106. doi:10.1002/ijc.27886.

2 Roh V, Hiou-Feige A, Misetic V, et al. The transcription factor FOXM1 regulates the balance between proliferation and aberrant differentiation in head and neck squamous cell carcinoma. J Pathol. 01 2020;250(1):107-119. doi:10.1002/path.5342.

3 Qadir F, Aziz MA, Sari CP, et al. Transcriptome reprogramming by cancer exosomes: identification of novel molecular targets in matrix and immune modulation. Mol Cancer. Jul 2018;17(1):97. doi:10.1186/s12943-018-0846-5.

4 Teh MT. FOXM1 coming of age: Time for translation into clinical benefits? Perspective. Frontiers in Oncology. 2012-October-15 2012;2(146):1-6 (10.3389/fonc.2012.00146). doi:10.3389/fonc.2012.00146

5 Teh MT. Initiation of Human Tumourigenesis: Upregulation of FOXM1 Transcription Factor. In: Hayat MA, ed. Stem Cells and Cancer Stem Cells,Volume 3. Springer Netherlands; 2012:149-154:chap 14. Stem Cells and Cancer Stem Cells.

6 Gemenetzidis E, Costea DE, Parkinson EK, Waseem A, Wan H, Teh MT. Induction of human epithelial stem/progenitor expansion by FOXM1. Cancer Res. Nov 15 2010;70(22):9515-26.

7 Teh MT, Wong ST, Neill GW, Ghali LR, Philpott MP, Quinn AG. FOXM1 is a downstream target of Gli1 in basal cell carcinomas. Cancer Res. Aug 15 2002;62(16):4773-80.

8 Ma H, Dai H, Duan X, et al. Independent evaluation of a FOXM1-based quantitative malignancy diagnostic system (qMIDS) on head and neck squamous cell carcinomas. Oncotarget. Aug 23 2016;7(34):54555-54563. doi:10.18632/oncotarget.10512.

*Note: This is a commercial profile

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2020-11-15T09:08:56-07:00November, 2020|Oral Cancer News|
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