| Overwhelming evidences demonstrated that dendritic cells (DCs), the most potent professional antigen presenting cells (APC), which expressed high levels of MHC class I and II and costimulatory molecules, were efficient in phagocytosing antigens, migrating to lymphoid organs, and presenting antigens to naive T cells. The unique ability of DCs to induce and sustain primary immune responses made them optimal candidates for vaccination protocols in cancer immunotherapy.DCs played an important role in initiating innate and adaptive immune responses, especially the potent antitumor immunity. Immature DCs had specialized antigen uptake and processing machineries, whereas mature DCs had an extraordinary capacity to present antigens and stimulate naive T cells. Functionally, mature DCs were 100 times more potent than macrophages in activating naive T cells in vitro. DCs loaded with appropriate tumor associated antigen (TAA) could induce protective/rejection immune responses in animal models and promising preliminary data are reported in human. Several systems had been used to deliver TAA to DCs, including (1) defined peptides of known sequences, (2) undefined acideluted peptides from autologous tumors, (3) whole tumor lysates, (4) retroviral and adenoviral vectors, (5) tumor cell-derived RNA, (6) fusion of DCs with tumor cells, and (g) exosomes derived from DCs pulsed with tumor peptides (subcellular structures containing high levels of MHC molecules and peptides).In order to induce DCs maturation and trigger their transitions from immature Ag-capturing cells to mature Ag-presenting cells, various cytokines or biological factors were applied, such as CD40 ligand (CD40L) on activated T cells, soluble CD40L, CD40L transfectants or agonist mAbCD40, tumor necrosis factor-a (TNF-a), IL-1b, lipopolysaccharide (LPS), unmethylated CpG DNA sequences, double-stranded RNA(dsRNA), nucleotides (ATP, UTP), and heat shock proteins (HSP). Notably, studies demonstrated that CD40 stimulated DCs (either cross-linked by agonists mAbCD40 or ligated by soluble CD40L and CD40L transfectants) were most potent to induce antitumor immunity. Moreover, several reports suggested that DCs could not stimulate cytotoxic T lymphocytes (CTL) unless they were firstly stimulated via CD40 on their surface. TNF-a, as a standard cytokine to induce DCs maturation, was inferior in conditioning DCs to activate tumor specific immune response, particularly CD8+ CTL, compared with CD40L. However, DCs-mediated induction of immunity represented a challenge, and several parameters needed to be considered to ensure the optimal outcome of DCs based vaccination protocols including the source of TAA, the methods for TAA preparation and loading, and the diversity of DCs subsets, et al. It was crucial and useful to discern the biological characteristics of CD40 ligation DCs or TNF-a stimulation DCs, as DCs vaccines were applied in many clinic trials.Part I : Roles of idiotype immunoglobulin pulsed dendritic cells in B cell iymphoma's immunotherapyEach B lymphocyte expressed a clonal immunoglobulin (Ig) whose heavy and light chain variable regions (VH and VL, respectively) comprised a unique collection of antigenic determinants known as the idiotype immunoglobulin (Id). B cell malignancies, as low grade non-Hodgkin's lymphoma (NHL), presented an opportunity of tumor specific immunotherapy because Id was maintained following B lymphocytes' malignant transformation. Id containing sequences epitopes which could be recognized by antibodies, CD4+ and CD8+ T cells was regarded as a useful TAA of B cell lymphoma.Objective: Our study aimed to investigate the role of Id-DC vaccine in B cell Iymphoma's immunotherapy.Methods: Balb/c mouse B cell lymphoma cell lines were obtained by fusing SP2/0 cells with Balb/c mouse spleen cells after immunization with pristane and incomplete Freund's adjuvant (IFA) respectively. Enzyme-linked immunosorbent assay (ELISA) and flowcytometry (FCM) were used to screen the secreting Id clones and analysis the phenotypes...
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