A Decade in the Making: HKUMed Scientists Achieve Cancer Vaccine Breakthrough
Researchers from HKUMed have found that tiny particles secreted by immune cells offer a promising pathway to an off-the-shelf cancer vaccine.
Led by Professor Tu Wenwei, an immunologist in the Department of Paediatrics and Adolescent Medicine, the findings build on more than a decade of research examining the potential of a subset of T cells, a type of immune cell, to fight tumours.
The Hong Kong-based group is among a growing number of global research teams exploring vaccines to combat cancer. Unlike the vaccines used to protect from viruses such as influenza or measles, which prevent disease, most cancer vaccines are therapeutic, meaning they train the patient’s immune system to fight an existing cancer.
Many of these teams have explored the use of dendritic cells (DCs)-based tumour vaccines. These are based on differentiation from peripheral blood monocytes or hematopoietic progenitor cells from bone marrow.
This route is not ideal as it is both expensive and difficult to produce the personalised DCs needed to create the vaccine, Professor Tu said. Additionally, the efficacy of cell-based vaccines is limited by the immunosuppressive tumour microenvironment.
However, the HKUMed researchers have chosen a different approach.
Their work focuses on γδ-T cells, a type of white blood cell, known for their direct anti-tumour activity and the ability to enhance T cell responses. In their latest study, the research team focused on nanoparticles secreted by human γδ-T cells known as γδ-T-derived exosomes to overcome the limitations of cell-based vaccines.
Earlier research by Professor Tu’s team showed some tumours were resistant to treatment with γδ-T cells, highlighting the challenges of penetrating a tumour’s defences and prompting the team to find alternatives.
“Live cells such as γδ-T cells and CAR T cells [Chimeric Antigen Receptor T cells] have a problem that the tumour microenvironment will try to compromise their attack,” Professor Tu said, referring to the technology where a patient’s T cells are manipulated in the laboratory to attack cancer cells.
“For immune cell exosomes, they have similar effects to their parent cells, so we thought about using γδ-T cell exosomes, because we had proven γδ-T cells could kill tumour cells.”
Breakthrough discovery
Their findings showed the nanoparticles exhibited dual anti-tumour activities by both directly killing Epstein Barr Virus-associated tumour cells and stimulating the immune system to recognise and attack tumour cells.
Importantly, the researchers also found that loading the γδ-T-derived exosomes with tumour-associated antigens to create a tumour vaccine produced a greater tumour-specific T-cell response than using the exosomes alone. This finding offers a promising new avenue for a potential cancer vaccine.
“Our group is the first team to publish data demonstrating γδ-T cells exosomes have anti-tumour activities, both in killing tumour cells and enhancing tumour-specific T cell responses,” the immunologist said.
Professor Tu, who describes γδ-T cells as his favourite type of cell, completed his medical training in mainland China. Originally planning to train to become an intensive care doctor, he was persuaded to explore immunology as the specialty offered a greater opportunity to gain overseas experience.
He went on to complete his PhD at the University of Hong Kong in the Department of Paediatrics and Adolescent Medicine focusing on paediatric immunology, especially primary immunodeficiency diseases. He went on to work at Stanford University before returning to HKUMed
Cancer vaccine game changer
The team’s latest study showed the use of γδ-T cell exosomes had several benefits over other technologies currently being examined for cancer vaccines.
Crucially, they found that allogeneic γδ-T cell exosomes, those derived from healthy donors, had similar preventative and therapeutic effects to those derived from the patient’s own cells.
This, combined with the fact exosomes are more stable than live cells, would allow for centralised and standardised production, removing the need for more expensive, personalised vaccines.
Additionally, Professor Tu said the technology is potentially simpler and cheaper than alternative immunotherapy and vaccine technologies such as CAR-T cell therapy and DCs-based vaccines.
From benchside to bedside
Following these findings, Professor Tu said the technology has the potential to become a universal platform for cancer vaccines or anti-cancer therapy.
He explained that γδ-T cell exosomes can be loaded with different tumour-associated antigens to treat a variety of cancers, in what he described as a “cocktail”.
Professor Tu is now working to raise funds for a start-up company to advance this work, alongside efforts to carry their findings through to clinical trials.
He added that an early focus will be testing the technology’s efficacy against Epstein Barr virus-associated cancers, which account for around 2 percent of cancer deaths around the world.
Professor Tu also plans to conduct trials on other common cancers such as of the lung, liver, gut and breast in complement to existing treatments such as chemotherapy and radiotherapy.
He is now in discussion with pharmaceutical companies to translate the team’s findings from the benchside to the bedside with clinical trials.
“We hope we can produce something that’s a first-in-class off-the-shelf anti-tumour product.”
