Immune therapy including dendritic cell based therapy in chronic hepatitis B virus infection

Abstract

Hepatitis B virus (HBV) infection is a global public health problem. Of the approximately 2 billion people who have been infected worldwide, more than 400 million are chronic carriers of HBV. Considerable numbers of chronic HBV carriers suffer from progressive liver diseases. In addition, all HBV carriers are permanent source of this virus. There is no curative therapy for chronic HBV carriers. Antiviral drugs are recommended for about 10% patients, however, these drugs are costly, have limited efficacy, and possess considerable side effects.Recent studies have shown that immune responses of the host to the HBV are critically involved at every stage of chronic HBV infection: (1) These influence acquisition of chronic HBV carrier state, (2) They are important in the context of liver damages, (3) Recovery from chronic HBV-related liver diseases is dependent on nature and extent of HBV-specific immune responses. However, induction of adequate levels of HBV-specific immune responses in chronic HBV carriers is difficult. During the last one decade, hepatitis B vaccine has been administered to chronic HBV carriers as a therapeutic approach (vaccine therapy). The present regimen of vaccine therapy is safe and cheap, but not so effective. A dendritic cell-based therapeutic vaccine has recently been developed for treating chronic HBV infection. In this review, we will discuss about the concept, scientific logics, strategies and techniques of development of HBVspecific immune therapies including vaccine therapy and dendritic cell-based vaccine therapy for treating chronic HBV infection.

B7-H1 Up-Regulation on Myeloid Dendritic Cells Significantly Suppresses T Cell Immune Function in Patients with Chronic Hepatitis B

“…These data suggest that B7-H1 up-regulation on mDCs may be responsible for the defective HBV-specific T cell function in chronic HBV infection. In addition, Ag-or virus-pulsed autologous MoDCs have recently shown great clinical therapeutic potentials in HIV (11) and HBV (12,44) infection. Thus, blockade of B7-H1 may improve the efficiency of MoDC-based therapeutic vaccine for CHB.…”

Lymphoid tissue–specific homing of bone marrow–derived dendritic cells

“…1 DCs may be generated in large numbers in vitro from progenitor cells, and modified to either boost an immune response against tumors or microbes, or dampen an autoimmune or allergic response, in many cases in an antigen-specific manner. Therefore, immunotherapy with DCs represents a new generation of potent personalized medicine to fight various cancers, 2-4 chronic infectious diseases, [4][5][6] and possibly autoimmune diseases. 7,8 The feasibility of such an approach has been established through many clinical studies (http://www.clinicaltrials.gov).…”

Uric acid enhances T cell immune responses to hepatitis B surface antigen-pulsed-dendritic cells in mice

“…T-cell mediated immune responses, especially Hepatitis B virus (HBV) specific-cytotoxic T lymphocyte (CTL) response, may play an important role in resolving HBV infection [1,2] . hepatitis B surface antigen (HBsAg) pulsed DCs can activate lymphocytes to become HBsAg-specific CTLs or specific CD4 + T cells in vivo [3] . Shimizu et al [4] immunized HBV transgenic mice with DCs loading HBsAg, and found that DC vaccine could break tolerance to HBV and induce an effective anti-viral immune response.…”

“…This may be due to the diversity of DC vaccine preparations; however, the main cause may be the insufficiency of DC vaccines. For example, some researchers carried out similar immune therapy in volunteers, but no evident immune response was shown [3,[6][7][8] . Therefore, the basic research of DC vaccine as well as how to improve the immune response to DC vaccine is still a significant challenge.…”