Patients with intermediate-stage hepatocellular carcinoma who received a vaccine of dendritic cells in addition to transarterial chemoembolization (TACE) and preconditioning cyclophosphamide experienced longer progression-free survival than those who received cyclophosphamide and TACE alone. The results of the ImmunoTACE trial were published by Ma et al in Clinical Cancer Research.
The collaborative study included the University of Birmingham, University Hospitals Birmingham, Nottingham University Hospitals NHS Trust, and Aintree University Hospital and Clatterbridge. Investigators 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 to stimulate immune responses against the cancer.
In the experimental arm of the trial, the average time to progression of the tumor was 18.6 months, compared with 10.4 months in the group who received standard treatment alone.
David Adams, MD, FRCP, FMedSci, Chief Investigator of the study and Emeritus Professor of Hepatology at the University of Birmingham, commented: “The results from this phase II trial are very promising and offer a potential new treatment option for patients with primary liver cancer, one of the highest causes of cancer-related death worldwide. 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 [in individuals] with liver cancer. The results warrant further investigation and could… offer much-needed hope and a better treatment option for patients.”
Dendritic Cell Vaccine
The vaccine is made with dendritic cells, which 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 the patients’ own white blood cells by growing them in a purpose-built laboratory for 8 days with proteins taken from cancer cells. The cells allow the immune system to see these proteins and then to mount an immune attack on the cancer cells that bear them. In ImmunoTACE, patients received the dendritic cell vaccine at the same time as standard treatment with chemoembolization and then monthly for a further 3 months.
Although dendritic cells are produced naturally in the body, studies have shown that in patients with cancer, 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 idea of the dendritic cell vaccine is 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, but the treatment did not significantly increase the incidence or severity of adverse events.
Lead study author Yuk Ting Ma, MRCP, PhD, Associate Clinical Professor at the University of Birmingham and an Honorary Consultant in Hepatobiliary Oncology at the University Hospitals Birmingham NHS Foundation Trust, said: “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.”
Dr. Ma continued: “Dendritic cell vaccines also represent a potential additional immune therapy to add to current checkpoint inhibitors. 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.”
Disclosure: For full disclosures of the study authors, visit aacrjournals.org/clincancerres.
