Patients with intermediate-stage hepatocellular carcinoma (HCC) who received a dendritic cell vaccine alongside standard treatment experienced nearly double the progression-free survival compared to those receiving standard care alone, according to results from the first clinical trial of its kind published in Clinical Cancer Research.
The ImmunoTACE trial, a collaborative phase II study led by the University of Birmingham and involving University Hospitals Birmingham, Nottingham University Hospitals NHS Trust, and Aintree University Hospital and Clatterbridge, recruited 48 patients who were randomly assigned to receive either standard treatment alone or standard treatment plus a cellular vaccine using dendritic cells loaded with cancer antigens.
Significant Improvement in Disease Control
In the experimental arm of the trial, the average time to tumor progression was 18.6 months, compared with 10.4 months in the group who received standard treatment alone. This represents a substantial improvement in progression-free survival for patients with primary liver cancer, which ranks among the highest causes of cancer-related death worldwide.
"The results from this phase II trial are very promising and offer a potential new treatment option for patients with primary liver cancer," said Professor David Adams, Chief Investigator of the study and Emeritus Professor of Hepatology at the University of Birmingham. "As far as we know, ImmunoTACE is the first controlled clinical trial to show that a cell-based vaccine using lab-grown dendritic cells can improve patient outcomes with liver cancer."
Novel Vaccine Approach
The vaccine utilizes dendritic cells, which naturally help orchestrate the immune system's response to diseases including cancer by activating immune killer cells to recognize and destroy cancer cells. The dendritic cells used in the study were expanded from patients' own white blood cells by growing them in a purpose-built laboratory for eight days with proteins taken from cancer cells.
This process allows the immune system to recognize these proteins and mount an immune attack on cancer cells that bear them. Patients received the dendritic cell vaccine at the same time as standard treatment with transarterial chemoembolization (TACE) and preconditioning cyclophosphamide, then monthly for a further three months.
Addressing Immune System Dysfunction
While dendritic cells are produced naturally in the body, studies have shown that in cancer patients they can become "exhausted" and stuck within the tumor rather than carrying cellular information back to the lymph nodes where they can activate immune killer cells. The dendritic cell vaccine aims to restore and uncover immune responses to the cancer.
An enhanced antigen (α-fetoprotein)-specific immune response was observed in patients treated with the vaccination, and importantly, the treatment did not significantly increase the incidence or severity of adverse events.
Future Clinical Applications
Dr. Yuk Ting Ma, lead author of the study and Associate Clinical Professor at the University of Birmingham, emphasized the broader implications of the findings. "These are very promising findings that demonstrate the potential use of dendritic cell vaccines in a widely prevalent and hard-to-treat cancer. With our approach to developing the vaccine, focusing on stimulation with multiple tumor antigens, we have shown a strong signal that we believe warrants testing in larger trials in patients with liver cancer."
The research team also highlighted the potential for combination approaches. "Dendritic cell vaccines also represent a potential additional immune therapy to add to current checkpoint inhibitors," Dr. Ma noted. "Future studies will look at whether adding dendritic cell vaccination to standard immunotherapy can derive better outcomes for patients with hepatocellular carcinoma who show only modest responses to current checkpoint inhibitor drugs."
The current trial design demonstrates that this therapy can be both affordable and effective, potentially offering much-needed hope and better treatment options for patients with this challenging malignancy. Hepatocellular carcinoma is a common type of liver cancer whose prevalence is increasing in the UK according to Cancer Research UK.
