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The latest on CAR T-cell therapy research

The latest on CAR T-cell therapy research

A clinical trial will test advancements in chimeric antigen receptor (CAR) T-cell therapy developed in Australia and funded by the Leukaemia Foundation*.

The clinical trial opened in Sydney in August 2017 for people with relapsed B-cell leukaemias and lymphomas, following TGA and ethics approvals.

CAR T-cells are a revolutionary form of treatment for B-cell malignancies. In people with previously incurable disease, across multiple clinical trials, T-cells have resulted in complete response (CR) rates of approximately 80% against B-cell acute lymphoblastic leukaemia (ALL), and 50% CR rates against chronic lymphocytic leukaemia (CLL) and B-cell non-Hodgkin lymphoma (B-NHL).

Yet access to this therapy is limited due to the cost and complexity of CAR T-cell generation.

Dr David Bishop, who is completing his PhD, funded by the Leukaemia Foundation’s National Research Program*, is investigating new methods of generating CAR T-cells to address these issues.

Leukaemias and lymphomas that arise from a subset of white blood cells called B-cells are among the most common forms of blood cancer.

Standard treatment for these conditions involves chemotherapy and rituximab, an antibody that specifically targets and destroys B-cells, as well as bone marrow transplants for those people who relapse or are high risk.

“Unfortunately, despite these treatment options, a subset of patients with highly aggressive leukaemia or lymphoma will have incurable disease,” said Dr Bishop.

In recent years, a ground-breaking new form of treatment for B-cell malignancies has been developed – CAR T-cell therapy.

“The normal role of a T-cell is to provide immunity against foreign invading pathogens, like bacteria and viruses. Because cancer cells arise from normal body tissue, naturally occurring T-cells have difficulty recognising them as abnormal,” Dr Bishop said.

“To overcome this problem, a synthetic CAR can be introduced into a naturally occurring T-cell by genetic modification, which enables it to recognise markers on the surface of B-cell leukaemias and lymphomas, and destroy them.

However, patients can only access CAR T-cells in clinical trials run in only a small number of centres worldwide.

“Factors contributing to this situation include the cost and complexity of CAR T-cell generation. My research has investigated new methods of generating CAR T-cells to address these issues, and also to improve CAR T-cell safety,” said Dr Bishop.

“We have developed a process that essentially cuts the CAR gene from a DNA template and pastes it into the T-cell genome.

“This has enabled us to reduce the cost of CAR T-cell production by 10-fold, to approximately US$10,000 per patient.

“We expect to open a clinical trial of these CAR T-cells at Westmead Hospital later in the year, for the treatment of patients with relapsed or refractory B-cell malignancies following allogeneic bone marrow transplant.”

Dr Bishop said another factor contributing to the cost of CAR T-cell therapy was the current need for every patient to have an individualised product, generated from their own T-cells.

“The main reason for this is to avoid graft-versus-host disease that could occur if CAR T-cells were generated from donor T-cells.

Because CAR T-cells, like any treatment, may have unwanted side-effects, Dr Bishop said it would be useful to be able to selectively eliminate them in the event of unacceptable toxicity.

“My research has explored incorporating a ‘suicide gene’ into CAR T-cells that sensitises them to the drug rituximab,” he said.

“When exposed to this drug, virtually all CAR T-cells expressing the suicide gene are eliminated, but ordinary T-cells are left untouched.

Dr Bishop said the CAR T-cell field was rapidly progressing globally.

“It is an incredibly exciting area of research to be involved in, and it’s very satisfying to see your ideas progress from a pre-clinical setting to being translated to the clinic where they can potentially have a meaningful impact on patient care.

“With a PhD scholarship, the Leukaemia Foundation has enabled me to take the first steps towards that goal by providing funding to undertake high quality research and share my findings with the world at international conferences,” said Dr Bishop.

*  Dr Bishop has a Leukaemia Foundation PhD Scholarship (Clinical) supported by the NSW Community Foundation, N&P Pinter, of $60,000 per year from 2014-2017 (Immune cell therapies for lymphoma, leukaemia and post-transplant viral infections).

World-first blood test could provide more effective, less invasive blood cancer treatments

World-first blood test could provide more effective, less invasive blood cancer treatments

A world-first “liquid biopsy” could soon offer you direct access to a simple blood test to help in the monitoring and management of your blood cancer treatment.

The blood test promises a new era of less invasive, more precise and effective management of your blood cancer, in place of painful bone marrow or lymph node biopsies. It was developed by Associate Professor Sarah-Jane Dawson and Professor Mark Dawson at the Peter MacCallum Cancer Centre in Melbourne.

Unlike traditional biopsies, the test can be used at any time during your treatment, with rapid adjustments easily made should a relapse occur or if there is failure to respond to a particular therapy.

Helping to pioneer the development Assoc. Professor Sarah-Jane Dawson said this world-first test for blood cancers will help to rapidly advance the availability of new precision medicines and targeted therapies as they are developed.

“Not only does this new test promise clinicians and patients a more timely and accurate understanding of whether a cancer treatment is working, it gives scientists the ability to quickly and effectively evaluate how clinical trial patients are responding to new life-saving therapies,” she said.

Professor Mark Dawson said the liquid biopsy also addresses one of the major limitations of the current approach to managing blood cancers.

“This test for blood cancer provides a much more comprehensive picture of how a patient is responding to their treatment.”

Prof. Dawson acknowledged that generous community support has driven the basic research that ultimately culminates in these discoveries.

“As clinicians we see every day the adversity caused by cancer,” said Prof. Dawson. “It’s a testament to how important the task at hand is that generous supporters use their personal experiences as inspiration to fund cancer research.”

“This development is an example of what our team has been able to achieve and I assure you that there is much more to come,” said Prof. Dawson.

The emergence of liquid biopsies as precision cancer trackers could significantly reduce the amount of time people spend in hospital and reduce overall costs to our health system.

The blood tests will be available within Australia from July and are expected to become a standard clinical tool in the near future.

15-year Holden partnership celebrated

15-year Holden partnership celebrated

Thursday, 15 June 2017

A brand new Astra, Trailblazer and Trax were unveiled at the recent joint celebration acknowledging Holden’s 15 years of support for the Leukaemia Foundation’s Patient Transport Program in Victoria, bringing their fleet support from 17 vehicles to 20.

Many of our amazing volunteer drivers, supporters of the service and special guest Beverley Brock shared the special occasion at Holden HQ.

Leukaemia Foundation CEO Bill Petch, said the stress of finding reliable transport to meet medical appointments among those facing blood cancer shouldn’t be underestimated.

“The reality for many Victorians diagnosed with blood cancer is a desperate dash to the city for life-saving treatment. They often find themselves in an unfamiliar place without a car or forced to navigate confusing city streets and heavy traffic looking for hospitals and parking.

“Public transport just isn’t safe for those so vulnerable to infection and constantly turning to friends and family or worrying about your car’s mechanical reliability during months of treatment can become a very real burden.

“That’s why Holden’s support is so critically important. They’re providing the vehicles that will help the Leukaemia Foundation drive people to the doctors and nurses and medicines that will save their life.

“I’d like to thank Holden for their ongoing support and providing three more cars that will soon be on the road with our trained volunteer drivers helping more Aussie families beat their blood cancer,” he said.

The Leukaemia Foundation Patient Transport Program began in Victoria, expanding to all states to support thousands of people facing blood cancer across Australia.

Just last year, the Patient Transport fleet travelled more than 1,500,000 km (that’s equivalent to 100 times around Australia).

Australians living with MPN step closer to accessing Pegasys treatment

Australians living with MPN step closer to accessing Pegasys treatment

The drug interferon alfa-2a (Pegasys®) was finally listed on the agenda of the Pharmaceutical Benefits Advisory Committee (PBAC) meeting on March 8 and many Australians are awaiting the results of the discussion.

For Nathalie Cook, who was diagnosed with MPN in 2008, this achievement was especially exciting after six years of dedicated campaigning for this drug to be made available in Australia.

Nathalie attended an MPN doctor-patient conference at the Mayo Clinic in the United States in 2011 where haematologists explained how the drug interferon can cause MPN patients to go into deep molecular remission and that the newer form of interferon – Pegasys – was easier to tolerate with fewer adverse side-effects.

“It was on the flight home that I made the decision to try to get Pegasys on the Pharmaceutical Benefits Scheme for people with MPN in Australia,” said Nathalie.

She began documenting her experiences and in 2013, Nathalie had the opportunity to start treatment with Pegasys. Within weeks her hair began to grow back and her flu-like symptoms diminished.

Returning to the Mayo Clinic MPN conference in 2013 and 2015, Nathalie stepped up her lobbying efforts and was rewarded with a letter from the Health Minister. It advised that her submission was being considered at the March 8 meeting of the PBAC.

Mustering support from the wider MPN community and haematologists across the country, Nathalie also welcomed a supporting PBAC submission by the Leukaemia Foundation.

Caroline Turnour, the Leukaemia Foundation’s General Manager, Research Advocacy and Services said Nathalie’s resolve has put Pegasys on the PBAC’s agenda.

“Our combined advocacy must continue,” said Caroline. “The path to PBS listing isn’t straight forward as Pegasys isn’t registered by the Therapeutic Goods Authority (TGA) for MPN and currently this can only be done by a pharmaceutical company.”

Until it is TGA registered doctors can only prescribe this drug ‘off label’.

“I expect the requirement for Roche to sponsor Pegasys’ registration for use by MPN patients will be one of the issues the PBAC discusses at this month’s meeting,” Ms Turnour said.

“We keenly await the outcome of this meeting and are committed to working with the Government and Roche to overcome any barriers that may stop it being listed.”

Nathalie continues to be in touch with the PBAC and is pleased to report that discussions are ongoing.

“I contacted Roche today to enquire about the outcome of this month’s (June ’17) meeting with Professor Wilson, Chair of the PBAC, following Roche’s feasibility assessment of Pegasys being made available for MPN’s on the PBS. Roche told me there was no definite outcome from this meeting however discussions are ongoing. I will continue to follow developments and report back to the MPN community when I hear anything more.”

* Interferon alfa-2a* (Roferon-A®) is listed on the PBS.