Chinese doctor’s near-miracle recovery after cancer immunotherapy shows the promise new treatment holds
Zou Yuliang was told he had weeks to live before taking part in a clinical trial for a new immunotherapy treatment that avoids targeting healthy B-cells. Now a new chapter of his life has opened up
In December Dr Zou Yuliang was told he had only weeks to live. Cancer had ravaged his body, spreading from his liver up to his lungs. Standard care had failed and he was struggling to breathe.
“We had no chance, not even for a liver transplant,” his wife, cardiologist Dr Zou Fanling, told the South China Morning Post.
But now Zou is not only recovered, he’s back at work and travelling around China for medical conferences – and it’s thanks to an extraordinary new cure that could change how we deal with cancer.
Zou’s stroke of good luck was linked to his own hospital. By sheer coincidence, it was exploring a new type of cancer immunotherapy called TCR Mimics in a clinical trial run by Eureka.
Immunotherapy is a game-changing cancer treatment that is based on harnessing the body’s immune cells to fight the disease. Existing immunotherapy treatments have shown promise in fighting blood cancers, as shown in the famous case of Emily Whitehead, a young American leukaemia sufferer saved by a type of immunotherapy treatment called CAR T-cell therapy.
With CAR T-cell therapy, a patient’s blood is collected and the T-cells (a type of white blood cell) separated to be genetically modified in a laboratory. A gene is inserted into the T-cells which causes them to make special receptor cells, called “chimeric antigen receptors” (CAR). These receptors specifically seek out antigens – toxins or other foreign substances which induce an immune response in the body – in cancer cells.
Millions of these modified T-cells are then grown before being infused into the patient so they can multiply, find and destroy malignancies.
This technique, however, has not yet worked on solid tumours such as breast, lung and liver cancers, which account for about 90 per cent of all cancer cases.
Another major drawback of CAR T-cell therapy is a targeting problem in that it kills normal healthy cells (B-cells) along with cancerous cells – a side effect that young Emily Whitehead suffered. For patients grappling with cancer in vital organs such as their liver or lungs, there cannot be a risk of wiping out healthy cells as well.
A decade ago, an idea was concocted to arm this therapy with an antibody that helped the immune cells better differentiate between solid-tumour cancer cells and normal solid-tissue cells, so that they would home in on – and annihilate – only the bad cells.
Existing T-cell therapy modifies the cells to recognise something on the surface of cancerous cells that denotes them as targets for destruction. But sometimes bad cells come in a different guise, or “plain clothing” rather than enemy uniform, Dr Cheng Liu, founder and CEO of Eureka Therapeutics in the United States and a friend of Dr Zou, explains.
Liu and David Scheinberg, a leukaemia specialist at the Memorial Sloan Kettering Cancer Centre (MSKCC), developed an idea to look inside enemy cells for something that could not be hidden: mutated oncogenes, or genes that turn normal cells into the cancerous kind.
“When that’s happening inside cells, there will be a small piece of that oncogene out and present on cells’ surface,” Liu explains, adding that this process is called “MHC peptide antigen presentation”.
Sceptics claim no technologies currently exist to detect such small oncogene fragments. But Liu and Scheinberg designed a special antibody that does just that. They called them “T-cell receptor (TCR) mimic antibodies”.
Eureka and MSKCC published their data in the journal Science Translational Medicine in 2013. Two years later they published a paper in the journal Nature Biotechnology that showed this antibody could be recruited into an immune system’s T-cells, redirecting the T-cell therapy to target solid tumours in a more effective fashion.
But would it work?
Liu focused this innovation on liver cancer. “Nobody at the time cared about liver cancer,” he says, adding that the disease’s high mortality rate and treatment difficulties deterred scientists from tackling it.
In animal testing models, the treatment cleared mice of liver cancer. Testing it on humans, however, was a challenge. “Nobody wanted to be the guinea pig,” Liu says. The ramifications were serious: if something went wrong – if subjects were killed in the process – his career and company would be finished.
Eventually Liu found an ally in China in Dr Chang Liu, a principal investigator and director of the surgical intensive care unit at The First Affiliated Hospital of Xian Jiaotong University. Chang Liu thought the innovation was worth exploring. The hospital’s president, Shi Bingyin, approved the clinical study.
This year, the immunotherapy was tried on six advanced liver cancer sufferers who had by then exhausted standard care options. During a nine-day process, the team extracted the patients’ T-cells, genetically modified them and multiplied the resulting TCR Mimic antibodies, then put them back into the patients.
The first subject was a farmer, bedridden in hospital as his cancer metastasised to his spine. To cope, he took painkillers daily. Three weeks after the treatment, the 65-year-old could walk again and stopped taking painkillers. CAT scans showed five tumours around his spine were gone.
He checked himself out of the hospital and returned to his rural hometown for Chinese New Year. However, a few days later, he died after ingesting hard food that caused intestinal bleeding. The cause, though, was deemed unrelated to liver cancer.
Zou, an oncologist – a doctor who treats cancer patients – heard about the farmer’s results and asked to participate in the study. In January, the 52-year-old underwent the therapy. By March, Zou was breathing better and could eat meat, which indicated improved lung and liver function.
However, his test results showed otherwise. CAT scans showed four masses in one of his lungs had grown. It was the darkest day of Cheng Liu’s life. “I thought: oh my god, was my first farmer patient a fluke?” he recounts.
In April, Zou’s biomarkers improved. A blood test on AFP – or alpha-fetoprotein, which measures a protein secreted from liver tumours – showed his levels had halved, after doubling the month before. In July, his AFP dropped to a normal range. CAT scans showed his lung tumours had shrunk; by the sixth month, they cleared.
No side effects were observed in any of the patients, with Cheng Liu explaining that healthy cells such as B-cells were not killed in the process. He presented the China clinical study data at the CAR-TCR Summit in Boston on September 5.
Cheng Liu explains that there are still a number of unknowns regarding this technique, including relapses in patients who are still being monitored.
Watch: How Hong Kong women fight cervical cancer
“I wouldn’t say I found all the answers to all the problems … what’s very promising is we are able to crack open the solid tumour field,” he says.
Eureka plans to start clinical trials in the US next year, which is the next step in the US Food and Drug Administration’s process to get the treatment to market.
A breakthrough like this could prolong the lives of those currently facing poor prognoses. In Hong Kong it could potentially end liver cancer’s ranking as the city’s No. 3 cancer killer.
According to the American Cancer Society, when cancer is localised in the liver, the five-year survival rate is 31 per cent. But when it spreads to distant organs or tissue, that rate drops to about 11 per cent.
Zou’s wife feels confident her husband is cured. The couple celebrated by taking their families to Chengdu, their favourite travel destination.
This time the holiday felt even more special. “Everything feels different to us now, everything feels new and we are appreciative,” she says. “Now we are happier together.”