Dendritic Cell Vaccine for Treating Hepatocellular Carcinoma

Mount Sinai Health System Background
Hepatocellular carcinoma (HCC) is the fifth leading cancer and third leading cause of cancer-related mortality worldwide. Surgical resection and liver transplantation remain the mainstay of effective therapy for patients with early disease. Even among the smaller subset of patients who are eligible for liver transplantation or surgical resection, high rates of post-operative cancer recurrence and progression to advanced disease remain a difficult problem. No treatments have demonstrated survival benefit in the adjuvant setting. Advanced disease is associated with poor outcomes with limited treatment options available to patients at this stage of disease. Thus a demand for novel non-surgical treatments persists in the clinical management of HCC, and strategies utilizing optimized immunotherapy are needed.
Technology Overview
Dendritic cell vaccination is recognized as an immunotherapy modality with potential for effective treatment of cancer. HCC is not clinically well established as an immunotherapy-responsive tumor. However, several levels of evidence suggest an important role for anti-tumor immunity in HCC biology. This technology provides the potential for a highly effective vaccine for use in HCC. The vaccine is prepared using autologous tumor cells and dendritic cells (DCs) enriched from bone marrow. DC’s are matured in vitro using a highly effective soluble factor, and loaded with antigen from autologous tumor cell lysates. The vaccine is delivered as systemic therapy following intravenous infusion.
Further Details
Wang et al – Autologous Tumor Cell Lysate-Loaded Dendritic Cell Vaccine Inhibited Tumor Progression in an Orthotopic Murine Model for Hepatocellular Carcinoma. Ann Surg Oncol. 2016 Dec;23(Suppl 5):574-582
Stage of Development
Extensive experience with a preclinical murine model indicates that this vaccine significantly increases survival of test animals, by reducing the proportion of immunosuppressive regulatory T cells (Treg) within the tumor. Response to the vaccine has been validated by non-invasive imaging methods, serum tumor marker experiments, and assays of immune cell sub-populations in the tumor micro-environment of test animals. Experiments with HCC specimens have validated the hypothesis that Treg infiltration also occurs in human HCC, and that Treg numbers correlates with survival of HCC patients.
Benefits

Potential for a highly effective personalized vaccine to treat HCC
Favorable safety profile

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