Delivery of a dendritic cell vaccine as part of standard of care chemotherapy for patients with liver cancer – the ImmunoTACE trial
Stuart M Curbishley*, Miroslava Blahova, Yuk Ting Ma, David H Adams
NIHR Birmingham Liver Biomedical Research Unit, University of Birmingham, Edgbaston, Birmingham. B15 2TT
Introduction: As a consequence of the increased prevalence of cirrhosis the incidence of hepatocellular carcinoma (HCC) is rising. We have previously demonstrated tumour-pulsed dendritic cells (DC) can induce effective T cell responses, are well tolerated and can be localized to the liver by intra-arterial infusion. Here, we describe a clinical trial delivering DC vaccination alongside standard of care chemotherapy.
Methods: Peripheral blood monocytes (Mo) are selected from apheresis products by semi-automated magnetic bead selection (Miltenyi Biotec, CliniMACS Prodigy) before differentiation into immature Mo-DC. After 5 days in culture, cells are antigen loaded and matured by the addition of monophosphoryl lipid A, a potent Toll Like Receptor-4 agonist. After a further 40 hours in culture, the mature Mo-DC are harvested and cryopreserved. Eligible patients are pre-conditioned with low-dose cyclophosphamide to deplete regulatory T-cells before receiving DC vaccination. The initial vaccination is given directly into the hepatic artery at the time of Trans-Arterial-Chemo-Embolisation (TACE). Follow up vaccinations are given monthly for the next 3 months via a peripheral vein.
Results: To date, four patients have received a total of 16 vaccinations without adverse event. Immunophenotypic analysis of peripheral blood samples reveals reduction in Treg frequency following cyclophosphamide induction with additional variations after TACE. Increase in tumour associated antigen-specific T-cell responses can be detected after treatment.
Conclusion: The ImmunoTACE clinical trial demonstrates the feasibility of delivering bespoke cellular therapy vaccines alongside standard of care treatment. Lessons learnt from these early studies will streamline the integration of cell-based immunotherapy into mainstream cancer treatment.