New research to improve human immune system's ability to fight cancer

Research that aims to understand and improve the immune system’s ability to fight cancer has been given a boost with funding support of $628,152 awarded to scientists at the Olivia Newton-John Cancer Research Institute (ONJCRI).

The funding, awarded by the National Health and Medical Research Council (NHMRC) of Australia and announced today, will support the work of Dr Miles Andrews and Dr Eliza Hawkes for the next four years.

Dr Andrews, a researcher and clinical oncologist, has been awarded the NHMRC CJ Martin Overseas Biomedical Fellowship to better understand which cancer patients will respond best to immunotherapy.

He will spend the first two years of his fellowship at the MD Anderson Cancer Center in Houston, Texas, before returning to ONJCRI, where he completed his PhD in September 2016.

Dr Andrews will use his fellowship funding to better identify those cancer patients who will benefit from therapies that boost the immune system’s ability to fight cancer.

“The past 5-10 years have seen significant advances in the use of immunotherapy in cancer treatment,” Dr Andrews said. “However immunotherapy is not used in treating the majority of cancers so many patients have not had the opportunity to benefit from it.”

Dr Andrews aims to identify biomarkers that will give doctors better insights into which patients will respond well to immunotherapy.

Dr Hawkes, an honorary clinician researcher at ONJCRI, has been awarded an NHMRC health professional research fellowship to further her research into immunotherapy as a treatment for patients with lymphoma.

Lymphoma is the fifth most common cancer in Australia. Dr Hawkes will use her fellowship to evaluate immunotherapy as a treatment for three different types of lymphoma: diffuse large B-cell lymphoma, Hodgkin lymphoma, and follicular lymphoma.

“Early stage clinical trials suggest that immunotherapy is effective in treating patients who have had a lymphoma relapse, however it is not used routinely in these patients,” Dr Hawkes said. “My research will evaluate the effectiveness of new immunotherapies in treating patients with diffuse large B-cell lymphoma, Hodgkin lymphoma, and follicular lymphoma.”

Minimising the side effects of breast cancer treatments

Dr Belinda Yeo is working to personalise breast cancer treatment, saving women the potentially harmful side effects that go with unnecessary treatments.

If breast cancer is caught early, the vast majority of women will survive and not endure it again. But despite the fairly low risk of cancer recurring, many patients endure ongoing post-surgery treatment including chemotherapy with its potentially harmful side effects and anti-oestrogen therapy, as ‘insurance’ against the cancer.

Belinda wants to find better tests to estimate the risk of a patient’s breast cancer returning. If the risk is low, it means those patients can avoid treatments they don’t need and they won’t have to live with the side effects they can cause.

“Of course, we want to cure our patients but we don’t want to cause them harm for the rest of their lives, and remember, many of these women have many years to live,” Belinda says. “Ultimately, we want to maximise survival and minimise toxicity.”

The side effects of cancer treatments can be severe. Chemotherapy might cause nausea and vomiting, fatigue, hair loss, menopausal symptoms or depression, or more serious problems. Five or more years of anti-oestrogen therapy can ruin sleep, wither a woman’s libido, bring on early menopause, affect fertility and make bones brittle.

Belinda is part of a drive to find better tests to understand each patient’s breast cancer at an individual genetic level. Doctors can use this information to predict how a patient will respond to different treatments, and to estimate the risk of a patient’s breast cancer returning. They can then personalise a treatment plan that is most effective for that patient, and if there is only a low risk of the cancer returning, the patient can avoid treatments they won’t benefit from.

“I’d like to move towards an era where we target our treatments more precisely to those women who have the most to gain from them, and spare women who have little to gain,” Belinda says.

Belinda works as an oncologist at Austin Health and clinical scientist at ONJCRI’s Translational  Breast  Cancer Program, which investigates a number of different breast cancers. She’s part of the Institute’s longstanding tradition of embedding researchers and clinicians in teams.

She also likes to include her patients in the process of translating laboratory findings into clinical practice, actively involving them in exploring their cancer and potential treatments.

Olivia Newton-John Cancer Research Institute Statement on Marriage Equality

The Olivia Newton-John Cancer Research Institute values diversity and inclusion and the many freedoms that are integral to a free, fair and equitable society. Through our research we endeavour to improve the lives of all Australians.

We are committed to providing a safe, compassionate and supportive environment for our staff and patients. We recognise the marriage equality debate is having negative impacts on the lesbian, gay, bisexual, transgender, intersex and queer (LGBTIQ) community. We extend our support and solidarity to the LGBTIQ community and their families and friends, and acknowledge their right to live in a society free of discrimination and prejudice.

The Institute strives to promote equity in our workplace and the medical research sector. We therefore support marriage equality which will provide our LGBTIQ staff, students and community with the same right afforded to others: the right to marry the person they choose.

Virus-antibody combo shows promise for treating advanced melanoma

Olivia Newton John Cancer Research Institute

A new treatment that combines an antibody with a cancer-killing virus improves outcomes for patients with advanced melanoma, an international clinical trial has shown.

The international study, led in Australia by Prof Georgina Long from the Melanoma Institute Australia in Sydney and Prof Jonathan Cebon from the Olivia Newton-John Cancer Research Institute (ONJCRI) in Melbourne, trialled the drug combination after it was found that only some patients with advanced melanoma responded to an antibody called pembrolizumab.

Pembrolizumab boosts the immune system’s ability to attack tumours by blocking a cell surface protein called PD-1, Prof Cebon said.

“However, when you give pembrolizumab to melanoma patients, only a small percentage of patients respond,” he said. “Studies of these patients suggested that they were more likely to respond to pembrolizumab if their tumours had pre-existing inflammation.”

To test this idea the researchers injected a cancer-killing virus called talimogene laherparepvec (TVEC) into melanoma patients’ tumours to create an inflammatory micro-environment., while at the same time treating them with pembrolizumab.

The results of the study have been published today in the journal Cell.

Twenty-one patients participated in the phase 1b clinical trial, the majority from Melanoma Institute Australia in Sydney. Additional patients were recruited from the Olivia Newton-John Cancer Wellness and Research Centre in Melbourne and from other hospitals around the world.

Prof Long said the trial results suggested that injecting the oncolytic virus into the tumours increased the ability of cytotoxic T cells (a type of white blood cell that kills cancer cells) to infiltrate the tumour and therefore may improve the antitumor activity of pembrolizumab.

“62% of patients had a response and 33% had complete disappearance of their melanoma,” Prof Long said. “We are now doing a clinical trial of the TVEC/pembrolizumab combination compared with pembrolizumab alone in large numbers of patients with advanced melanoma. This should confirm whether TVEC enhances the activity of pembrolizumab.”

The clinical trial was cosponsored by pharmaceutical companies Amgen and MSD.

Publication details: Ribas A, Dummer R, Puzanov I, et al. Oncolytic Virotherapy Promotes Intratumoral T Cell Infiltration and Improves Anti-PD-1 Immunotherapy [published correction appears in Cell. 2018 Aug 9;174(4):1031-1032]. Cell. 2017;170(6):1109-1119.e10. doi:10.1016/j.cell.2017.08.027

New generation melanoma treatment could remove unwanted side effects

(L) Mr Dani Tutuka, (Centre) Prof Jonathan Cebon, (R) Dr Andreas Behren

An unwanted side-effect of a standard treatment for advanced melanoma could be overcome by a new generation of anti-cancer compounds, scientists at the Olivia Newton-John Cancer Research Institute (ONJCRI) have found.

About half of all advanced melanomas have a mutation in a gene called BRAF which drives the proliferation of the cancer. It is standard for people with BRAF-driven melanoma to be treated with targeted compounds called BRAF inhibitors.

Although these BRAF inhibitors work in most people with BRAF-mutated melanoma and block signals leading to cancer cell proliferation, paradoxically, they can also inadvertently trigger the same signaling pathway in non-melanoma cells thereby promoting the development or growth of other secondary cancers, including colorectal cancers. To prevent this from happening patients are treated with a second compound that stops this cell signaling pathway from being unintentionally activated. However, this may not be enough to always prevent the emergence of secondary cancers or their precursors.

Dr Andreas Behren, who led the ONJCRI research team, said that although extremely rare, it couldn’t be predicted which melanoma patients might develop other cancers as a result of their treatment. “A new generation of BRAF-inhibiting compounds termed ‘paradox breakers’ has therefore been developed in the hope of avoiding these unwanted side effects,” he said.

Dr Behren, Prof Jonathan Cebon, Mr Dani Tutuka and others from the ONJCRI examined whether these new-generation BRAF inhibitors could be successfully used to treat melanoma patients without unintentionally accelerating the growth of other cancers, including colorectal cancers.

Their research is published in the current issue of the journal Molecular Cancer.

Dr Behren said the ‘paradox breaking’ compounds were tested on BRAF melanoma cells for their potential to inhibit their growth and, after being seen to successfully target these cells, were then tested for their growth-promoting effects on various colorectal cancer cells in comparison to the classical drugs.

“We found that these new-generation paradox-breaking BRAF inhibitors did not promote or accelerate the growth in the colorectal cancer cells and may therefore, pending the results from ongoing clinical trials, be a safer alternative to be used alone or in combination in melanoma patients,” Dr Behren said.

The research was supported by the Melanoma Research Alliance, the National Health and Medical Research Council of Australia, Cancer Council Victoria and the Victorian State Government Operational Infrastructure Scheme.

Donors and researchers team up against deadly disease

Mesothelioma is cancer caused primarily by exposure to asbestos. It’s a deadly disease and there has been no treatment breakthrough in 14 years. But thanks to generous philanthropic grant funding, promising research at the Olivia Newton-John Cancer Research Institute (ONJCRI) may offer new treatment options.

Lyall Watts lost his life to mesothelioma in 2014. In the ten years since being diagnosed in 2004, Lyall became passionate about research into treatment and he desperately wanted researchers to find a cure. It was his one wish.

Before he died, Lyall set up a grant through Cancer Council Victoria to be used for research into mesothelioma treatment.  In Lyall’s honour, his partner Gary decided to continue the grant and name it the Lyall Watts Mesothelioma Research Grant. Lyall’s determination to find answers lives on through this grant.

A/Prof Tom John from ONJCRI was the inaugural recipient of this grant, and now together with Prof Andrew Scott, also from ONJCRI and Dr Peter James at Monash University, has received further funding from this grant to continue their work into targeted antibody therapies for malignant mesothelioma.

“We have a large tumour bank resource here at ONJCRI of patients who have donated their tissue,” says A/Prof John. “One of the things we have always wanted to do is put that resource together and use it to try to define markers within the tumour tissues that could predict response to particular treatments and identify new areas for further investigation.”

“The initial funding has allowed us to put together a resource that contains over 300 mesothelioma cases. It’s the biggest series in the world and has ended up being a really valuable resource.”

That value has already been proven with the discovery that EGFR (epidermal growth factor receptor), a protein found on cancer cells, is very commonly found in mesothelioma tumour cells (about 70 - 80 per cent).

Prof Scott and his laboratory team at ONJCRI have discovered a way to target EGFR using antibody therapy.

“So far, this treatment in mice is proving to be very effective.  We’ve been able to show that if a tumour expresses EGFR and it’s treated with this targeted therapy, then the tumours shrink away,” says A/Prof John. “Mesothelioma doesn’t seem to have many targets so this actually looks like a very relevant and useful target.  Furthermore, trials have already been conducted at ONJCRI in other tumours that express EGFR.  We’re hoping to start recruiting patients to another clinical trial for this targeted therapy later this year.”

Ivanhoe East house sale benefits lung cancer research

A/Prof Tom John

The Olivia Newton-John Cancer Research Institute (ONJCRI) has benefitted from the auction of a home in East Ivanhoe on 27 May 2017.

The home in Wilfred Road was auctioned by Nelson Alexander Ivanhoe which, as part of the real estate business’s annual Foundation Day, donated professional fees of more than $19,000 from the auction to the institute’s lung cancer research program.

In 2017, lung cancer is expected to kill more than 9000 Australians, making it the leading cause of cancer death in Australia.

The head of ONJCRI’s lung cancer research laboratory, A/Prof Tom John, said there was an urgent need for research into the disease as only 15% of people diagnosed with lung cancer were expected to live five years beyond their diagnosis.

“Lung cancer is the biggest cancer killer in Australia, indeed in the western world, yet very little is spent on lung cancer research,” A/Prof John said. “Recent studies have successfully shown that targeted therapies, and now immunotherapies, can work in a minority of patients to slow down the disease. These studies have highlighted that the more research that is done into a cancer, the greater the chance of developing new treatments and hopefully improving survival rates”

A/Prof John said the donation from Nelson Alexander would go toward discovering new targets for treatment. “The field of immunotherapy has generated some exciting results in people with seemingly incurable cancers,” he said. “With this funding we will explore why immune therapies work in only 30 per cent of people with lung cancer in the hope of making these therapies effective in all people with lung cancer.”

Nelson Alexander’s Foundation Day was established by the Nelson Alexander Charitable Foundation and is the day that each of the company’s 16 offices donates the professional fee from one of their auctions to the local community. Since its inception in 2005, the foundation has distributed more than $2 million.

Statement regarding Olivia Newton-John

The staff, students, volunteers and Board of the Olivia Newton-John Cancer Wellness & Research Centre, a partnership between Austin Health and the Olivia Newton-John Cancer Research Institute (ONJCRI), send Olivia their well wishes as she undergoes treatment following the relapse of her breast cancer, and are sending her positive thoughts for a speedy recovery.

Olivia, as the founding champion of the Olivia Newton-John Cancer Wellness & Research Centre (ONJ Centre), has long been committed to supporting wellness programs and improving the treatment and care of people with cancer through innovative research.

Prof Jonathan Cebon, the Medical Director of ONJCRI and of Cancer Services at Austin Health, said he was saddened to hear Olivia’s cancer had returned. “Late relapses from breast cancer can occur, especially for women with ‘hormone receptor-positive’ breast cancer,” Prof Cebon said. “These relapses can occur sometimes even decades after initial treatment for early breast cancer. This unpredictability of breast cancer, and its ability to return after many years, is an area of active research at the institute through our Translational Breast Cancer Program.”

Dr Belinda Yeo, who is leading this research, is trying to find better ways to estimate recurrence risk in patients diagnosed with hormone-receptor positive early breast cancer.

“Our laboratory is focused on how breast cancer cells first initiate spread to other parts of the body and why and how tumour cells that lie dormant for long periods of time can become active again,” Dr Yeo said.

“We are trying to better understand which women are at risk of late relapse events, so that their treatment can be tailored accordingly.”

Dr Yeo, who treats breast cancer patients through the ONJ Centre, said there were many treatments, including radiotherapy and various types of hormone therapy that could be very effective in treating late relapse. “Newer targeted therapies are providing significant improvements alongside standard therapies,” she said. “The ONJ Centre has several clinical trials investigating these novel targeted therapies for patients with metastatic breast cancer.”

New brain cancer drugs developed with Carrie Bickmore’s support

An antibody developed by scientists at the Olivia Newton-John Cancer Research Institute (ONJCRI) to treat the most aggressive form of brain cancer will be further refined following a generous grant from Carrie’s Beanies 4 Brain Cancer Foundation.

The grant, from the foundation established by television presenter Carrie Bickmore in honour of her first husband, who died from brain cancer, will support the work of Prof Andrew Scott and A/Prof Hui Gan.

Prof Scott and A/Prof Gan led the development of ABT-806, a unique antibody that targets glioblastoma multiforme (GBM), the most common and most aggressive form of adult brain cancer. Fewer than 10 per cent of people diagnosed with GBM are still alive five years after their diagnosis.

ABT-806 has since been combined with extremely potent cytotoxic drugs so these drugs can be delivered directly into brain tumour cells, A/Prof Gan said. “This antibody drug conjugate, called ABT-414, has been trialled on patients with GBM and shown remarkable results,” he said. “However, it does not work in all patients. With support from Carrie’s Beanies 4 Brain Cancer Foundation we are working on the second generation of these antibody-drug conjugates to improve their effectiveness and reduce side effects for people with GBM and other high-grade brain cancers.”

ABT-414 is currently in phase 3 clinical trials, the last step before being introduced as standard clinical care should the trials be successful. A/Prof Gan is leading the trials at Austin Health in Melbourne.

A/Prof Gan said the two years of funding from Carrie’s Beanies 4 Brain Cancer Foundation would not only allow the further development of ABT-414, but would also support research aimed at knocking out the network of cells that exist around brain tumours and that seem to support the development of the cancer.

“We are also developing antibodies and antibody-drug conjugates that target this tumour micro-environment, and have shown in the laboratory that it causes severe disruption to the tumour’s cellular support network,” A/Prof Gan said. “Targeting the tumour microenvironment in this way is an innovative approach to glioblastoma treatment that will may lead to improved outcomes Later this year we will begin recruiting patients with GBM for a clinical trial of an antibody targeting the tumour microenvironment at Austin Health in Melbourne and the Royal Brisbane and Women’s Hospital in Brisbane.”

Tumour breakthrough boosts gastrointestinal cancer hopes

(L) Dr Robert O’Donoghue, (Centre) Prof Matthias Ernst, (R) Dr Ashleigh Poh

Scientists at the Olivia Newton-John Cancer Research Institute (ONJCRI) have made a ground-breaking discovery that could progress the fight against gastrointestinal cancers, revealing a novel way to suppress the growth of tumours.

Gastrointestinal cancers – those that affect the stomach and bowel – are among the most common causes of cancer death, affecting more than 15,000 Australians each year.

The researchers have shown, in preclinical studies, that inhibiting a protein called HCK (hematopoietic cell kinase) can suppress the growth of established gastrointestinal tumours and reduce the emergence of new cancers.

Prof Matthias Ernst, who led the work with Dr Ashleigh Poh and Dr Robert O’Donoghue, said HCK had a powerful role in cancer development because of the effect it has on macrophages, a critical part of the immune system. “We have known for a long time that in non-cancer situations macrophages have two major roles;” Prof Ernst said. “These cells can behave like ‘garbage collectors’ when they remove unwanted debris or damaged cells, or they can behave like ‘nurses’ to help at sites of injury and wounding.

“What we’ve now discovered is the more HCK activity a macrophage has, the more it nurtures cancer cell growth and survival. The macrophage becomes a wound healer rather than a garbage collector that cleans up the cancer cells.”

Prof Ernst’s team found that inhibiting HCK using a small drug-like molecule reduced the growth of bowel and gastric cancers. Their work is published in the current issue of the international journal Cancer Cell.

Prof Ernst, who is the ONJCRI’s Scientific Director, said drugs that modify the behaviour of macrophages were already starting to show promise as a treatment for solid tumours.

“Our discovery could potentially offer a new and complementary approach to chemotherapy and immunotherapy as options for treating gastrointestinal cancers,” he said.

Dr Niall Tebbutt, Head of Medical Oncology at the Olivia Newton-John Cancer Wellness & Research Centre said the research presented important insight into future treatment approaches for gastrointestinal cancers. “Unfortunately, bowel cancer is generally resistant to conventional immunotherapy treatment,” Dr Tebbutt said. “This research may help us to understand why bowel cancer is so resistant to immunotherapy but, more importantly, it provides a new approach to possibly overcome this resistance through inhibition of HCK. Future clinical trials of this approach in patients with advanced bowel cancer are worth pursuing.”

The Victorian Minister for Health, Jill Hennessy, welcomed the research announcement. “Stomach and bowel cancers are among the biggest killers of Victorians each year and this revolutionary development has the potential to one day save thousands of lives,” Minister Hennessy said. “These ground-breaking results bring us yet another step forward in our fight against cancer, and once again it is researchers here in Victoria leading the way.”

The research was supported by the National Health and Medical Research Council of Australia, Ludwig Cancer Research, La Trobe University and the Victorian State Government Operational Infrastructure Scheme.

Publication details: Poh AR, Love CG, Masson F, et al. Inhibition of Hematopoietic Cell Kinase Activity Suppresses Myeloid Cell-Mediated Colon Cancer Progression. Cancer Cell. 2017;31(4):563-575.e5. doi:10.1016/j.ccell.2017.03.006