The research team, led by Professor Tu Wenwei (second right) and Professor Wang Weiping (second left), has made a breakthrough in cancer treatment by developing a new therapy which showed a significant reduction in melanoma growth, leading to more effective and safer treatments for cancers.
Researchers at the LKS Faculty of Medicine of the University of Hong Kong (HKUMed) have made a breakthrough in cancer treatment by developing a new therapy, called photosensitive hybrid γδ-T exosomes (hybrid γδ-T-Exos). This therapy targets and destroys cancer cells, while promoting the release of damage-associated molecular patterns (DAMPs) and boosting the subsequent antigen-specific immune response. In laboratory tests and animal studies, this innovative hybrid therapy showed a significant reduction in melanoma growth, leading to more effective and safer treatments for cancers. The findings were published in the scientific journal ACS Nano [Link to publication].
Background
γδ-T exosomes control tumours by inducing apoptosis and enhancing antitumour T-cell responses. When combined with antigens, they can function as tumour vaccines, as well as tiny carriers to deliver drugs. Unlike exosomes derived from dendritic cells (DCs) or natural killer (NK) cells, γδ-T exosomes stand out because they can target tumours, boost the immune system and be produced on a large scale, making them highly promising for cancer therapy. Photodynamic therapy (PDT), a minimally invasive treatment that is effective against melanoma, uses light to activate the photosensitiser to promote the production of reactive oxygen species (ROS) to attack cancer cells. By combining γδ-T exosomes with PDT, using Chlorine e6 (Ce6), researchers aimed to improve treatment effectiveness against melanoma.
Research methods and findings
The research team successfully developed photosensitive hybrid γδ-T-Exos by combining γδ-T exosomes with Ce6-loaded liposomes. The hybrid γδ-T-Exos retained tumour-targeting markers and cytolytic molecules, enabling precise targeting of melanoma cells.
In both laboratory experiments and animal studies, the hybrid γδ-T-Exos delivered drugs to melanoma cells more effectively than Ce6 liposomes alone. When exposed to light, they produced high levels of ROS, leading to immunogenic cell death (ICD) and stimulating robust immune response. In mouse models, the hybrid γδ-T-Exos significantly inhibited melanoma growth without harming normal organs or tissues, demonstrating excellent biosafety.
Professor Tu Wenwei from the Department of Paediatrics and Adolescent Medicine, School of Clinical Medicine at HKUMed, who led the research, said, 'This is the first time that γδ-T exosome therapy was combined with PDT. Hybrid γδ-T-Exos is a precise, efficient and immune-activating therapeutic strategy for treating melanoma, with great potential for clinical applications.'
Significance of the research
The findings of the study are highly significant for cancer therapy, especially in the field of photo-immunotherapy. By creating photosensitive hybrid γδ-T-Exos through membrane fusion with Ce6-loaded liposomes, the research team successfully combined two powerful anticancer strategies: PDT and γδ-T exosome therapy. This innovative approach preserves the immune-stimulating functions of γδ-T exosomes while boosting their therapeutic efficacy through ROS-mediated cytotoxicity from photosensitisers.
Hybrid γδ-T-Exos offer several key advantages. They enable precise tumour targeting through functional surface markers, effectively induce apoptosis and necrosis in melanoma cells, and activate systemic antitumour immunity by promoting dendritic cell maturation and T-cell responses. Unlike conventional treatments, this system minimises side effects by reducing off-target toxicity and provides long-term tumour control by fostering immune memory.
From a clinical perspective, hybrid γδ-T-Exos present a scalable and practical therapeutic option, as γδ-T cells can be expanded outside the body (ex vivo) and sourced from healthy donors, enabling standardised production. This simplifies the process compared to autologous therapies and paves the way for centralised manufacturing and wider accessibility. Beyond melanoma, this groundbreaking approach holds potential for treating other aggressive cancers, such as breast or colon cancer, significantly expanding its clinical applications and impact.
About the research team
The study was led by Professor Tu Wenwei from the Department of Paediatrics and Adolescent Medicine, School of Clinical Medicine, HKUMed, in collaboration with the team of Professor Wang Weiping, Associate Professor from the Department of Pharmacology and Pharmacy & Dr Li Dak-Sum Research Centre, HKUMed. The co-first authors were Gao Yifan, PhD student in Professor Tu's team, and Liu Jinzhao, PhD student in Professor Wang's team.
Acknowledgements
The study was supported by grants from the General Research Fund of the Research Grants Council of Hong Kong; the Health and Medical Research Fund of the Health Bureau, HKSAR; the Seed Funding for the Strategic Interdisciplinary Research Scheme of the University of Hong Kong; and the National Natural Science Foundation of China.
