Immunobiology and Gene-Based Immunotherapy of Hepatocellular Carcinoma

Abstract

Until now, a variety of specific and non-specific immunostimulatory strategies against HCC has been applied in preclinical experimental models with some promising results. The molecular characterization of HCC associated tumour antigens such as alpha-fetoprotein (AFP) and the increased understanding of the immunological pathways involved in liver and tumor immunology have paved the way for the design of promising gene-based cancer vaccines. The first phase I and II immunotherapeutic clinical trials based on dendritic cell immunotherapy and peptide vaccines are ongoing in HCC-patients. Clinical trials have, in general, demonstrated the safety of such strategies. Recently, exciting new immunological techniques and tools have been developed which allow to characterize antigen specific T cells at a single-cell level. In future, HCC specific tumor rejection antigens which can be used therapeutically have to be identified using microarray-based analysis. The different therapeutic modalities need to be compared directly resulting in optimised therapeutic approaches and the identification of sub-groups of HCC-patients responding favourably to treatment.

Thymostimulin versus placebo for palliative treatment of locally advanced or metastasised hepatocellular carcinoma: a phase III clinical trial

“…Immunomodulation is another promising strategy against HCC [8]. Thymostimulin - a standardized low-molecular protein fraction containing thymosin-α 1 and thymic humoral factor [8] - has been demonstrated to induce a selective, dose-dependent, cytotoxic immune reaction against HCC cell lines in vitro [9,10].…”

“…Thymostimulin - a standardized low-molecular protein fraction containing thymosin-α 1 and thymic humoral factor [8] - has been demonstrated to induce a selective, dose-dependent, cytotoxic immune reaction against HCC cell lines in vitro [9,10]. Based on the experimental data, two single-center phase II trials using thymostimulin in patients with locally advanced and metastasised HCC not amenable to or failing surgical and/or local therapy have been published including one by our group [11,12].…”

The Current State of Cancer Gene Therapy and Its Application in Esophageal Carcinoma

“…Nowadays, almost one out of three cancer gene therapy trials uses the immunotherapy approach (table 1). Phase II immunotherapeutic clinical trials based on dendritic cell immunotherapy for glioma and hepatocellular carcinoma patients are ongoing [15, 16] and a variety of melanoma tumor cell vaccines have been developed, including immunization with IL-7 [17] and IFN-γ [18]. …”