The life-saving jigsaw solved by science

The life-saving jigsaw solved by science

“If I was diagnosed five years earlier, I would not be alive today.”

In December 2017, life was good for Joshua Polon. He was a fit 31-year old man who loved going to the gym and working hard as a sales leader at Salesforce. He was in the best shape of his life.

Until one day, he woke up with an enlarged lump on his neck about the size of a tennis ball. When antibiotics had little effect, Joshua was sent for a biopsy and the results came back positive for stage 3 lymphoma. In an average, healthy body, lymphoma can be treated with chemotherapy. However, for Joshua, this approach was not successful.

After the first few cycles of chemotherapy, the tumours had barely shrunk. After intense chemotherapy, the situation for Joshua went from bad to worse. The tumours had still not shrunk and had, in fact, grown and spread. Joshua’s lymphoma was treatment resistant. A traditional bone marrow transplant was planned, but the chemotherapy required to prepare for that treatment was ineffective in controlling his lymphoma.

The prognosis for Joshua was devastating. He was told that he had a one in three chance to survive five years.

Instead of giving up hope, Joshua’s family began searching for relevant clinical trials. They came across a new clinical trial at Westmead Hospital, led by WIMR’s Associate Professor Ken Micklethwaite, and using CAR T cells. 

 WIMR’s Cell Therapies Group, who were involved in Joshua’s treatment, is led by Professor David Gottlieb, working alongside Associate Professor Micklethwaite and Associate Professor Emily Blyth who are senior research leads. 

CAR T cell therapy involves taking a patient’s own immune cells, reprogramming them in the laboratory to respond to a specific protein that is on the cancer cells. These cells are then infused back into the patient where they attack only the specific cancer cells.

Joshua was accepted into the CAR T cell clinical trial, but before this revolutionary treatment could commence, the medical team had to gain some control over Joshua’s tumours. To do this, they treated Joshua with another round of incredibly strong chemotherapy. Simultaneously, the team were preparing Joshua’s cells for CAR T cell therapy. 

“I ended up in intensive care and I didn’t come out for five weeks,” recalls Joshua. 

At the end of the cycle, for the first time since his diagnosis, Joshua’s tumours had finally shrunk. It was now safe enough to start the CAR T cell therapy. 

The four-month regime of CAR T cell therapy worked, and Joshua’s tumours slowly shrunk to only a few spots but did not completely disappear. Joshua went on to have radiation therapy and immunotherapy that finally brought his disease into remission.

Throughout his treatment, Joshua’s doctors had been investigating why his lymphoma was resistant to treatment. They discovered Epstein-Barr Virus (EBV) in Joshua’s tumour sample, and this was likely the main cause of the development of the cancer. EBV would also make a relapse of lymphoma very likely.

 To remain completely cancer-free, Joshua needed something more. The team decided to try a second bone marrow transplant done differently from the first and specifically targeting the Epstein-Barr Virus in Joshua’s lymphoma cells. The three biggest dangers for patients undergoing transplant are infection, disease relapse and a condition called graft versus host disease where the immune system from the donor attacks the patient and can make them unwell. The team at Westmead have been working on ways to address each of these risks separately, and painstaking clinical trials have been performed. 

Understanding the high stakes for Joshua, Professors Gottlieb, Blyth and Micklethwaite worked together to design a bone marrow transplant procedure that specifically targeted all the risks that Joshua faced using innovative cell therapy that has been developed at WIMR over decades. 

This included the last part of the puzzle which was to target the EBV. The team used tumour targeting immunotherapy, taking EBV-specific immune cells from Joshua’s bone marrow donor, his sister, and growing and strengthening them in the lab, before treating Joshua. This will hopefully keep the EBV driven cancer in remission. 

Despite many challenges, including more time in intensive care, the bone marrow transplant was a success.

Associate Professor Emily Blyth is a clinical and laboratory haematologist, blood transplant and cell therapies physician and the clinical lead for the Immune Effector Cell Service at Westmead Hospital. She is a research lead with the WIMR T Cell Therapies Group. Associate Professor Blyth said, “I am so happy that, in Joshua’s situation, we were able to put all the pieces of this intricate jigsaw together.  

“We’re at the stage now where we can link each of those technological advances together to create a patient specific transplant procedure. We need larger trials, but we are hopeful that this approach will prove to be a much safer and more effective way of treating these cancers.”

– Associate Professor Emily Blyth

Since March 2020, Joshua has been in remission and remained healthy. He is active and working full time, while planning for his upcoming wedding to his fiancée, Rachel.

Despite many hurdles, Joshua is incredibly grateful for WIMR’s CAR T cell and stem cell therapy research that made his survival possible. 

“If I had been diagnosed five years earlier, I would not be alive today,” said Joshua. 

“I am so unbelievably lucky that I was able to access exactly what I needed at the exact point in time of human history that it was available for use.” 

Associate Professor Blyth said the research that saved Joshua’s life requires more funding so it can continue to save many more lives. 

“Funding is crucial. There’s such a long way to go to improve outcomes for patients. Every patient is an individual, and we want to give each of these people the best chance of a healthy, cancer free future

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