| Carcinoembryonic antigen (CEA) is a heavily glycosylated oncofetal antigen that is overexpressed in human adenocarcinomas, especially in colon, pancreas, breast and lung, and, at a lower level, in normal adult colonic epithelium and other endodermally derived tissues. CEA represents a well-characterized oncofetal glycoprotein. The tissue expression pattern makes CEA a potential target for tumor specific immunotherapy. Recent studies have revealed that CEA-specific cytotoxic T lymphocytes (CTL) can be induced after the administration of CEA protein mixed with adjuvants, altered peptide of CEA, anti-idiotype antibodies of CEA, and CEA-based recombinant poxvirus vaccines. However, as a self-protein and due to immune tolerance, CEA is poorly immunogenic, thus more efforts should be put into exploring a successful strategy to improve the efficiency of CEA-based tumor immunotherapy.Hyperthermia is considered as a promising approach in cancer therapy, especially as a local regional treatment modality for certain solid tumors. Heat treatment per se can enhance the immunogenicity of tumor cells. Currently, it is thought that there are at least two mechanisms for enhancing anti-tumor immunity. One is high expression of HSP70, which may be associated with the processing and presentation of endogenous tumor antigens directly to tumor-specific T-cells; anotheris the augmentation of MHC-I expression on the tumor cells. A randomized phase III pilot study in human melanoma has been completed showing improvement of local tumor control and survival benefits in patients with multiple lesions after hyperthermia treatment. HSP are highly conserved proteins whose synthesis is indued under stress conditions, including heat stress. The accumulating evidences have demonstrated that tumor-derived HSP-peptide complexes can elicit antitumor response. Therefore, Hyperthermia, by up-regulating HSP70 or other stress proteins (e.g HSP110 and grpl70) and by causing local necrosis in tumor tissue, has the potential to directly activate the immune response against tumors.IL-18, previously known as IFN-γ-inducing factor, is also a promising vaccine adjuvant. IL-18 has a variety of effects on immune response including stimulating NK, T and B cells to express high levels of IFN-γ, promoting IL-2 secretion of the stimulated cells and inducing T-cell proliferation, enhancing killing activity of CTL and NK cells and up-regulating dentritic cell (DC) maturation. It also exerts pro-inflammatory properties by inducing the release of IL-1B, TNF-a, chemokines, and then chemoattract DC, T cells and polymorphonuclear cells. We and others have previously identified that IL-18 has potent anti-tumor immunity, mainly mediated by cytotoxic CD4~+, CD8~+ T cells and NK cells. IL-18 anti-tumor effects also involve FasL-mediated cytotoxicity and ihibition of tumor angiogenesis. Therefore, the pleiotropic activities of IL-18 suggest that this cytokine plays an important role in innate and adaptive immune responses, especially in anti-tumor immunity.Exosomes, described as membrane vesicles with a diameter of 30-90nm, can be released into the extracellular milieu upon the fusion of small internal compartments with the plasma membrane by many types of cells, such as mast cells, T and B lymphocytes, DC, platelets and tumor cells. Recently, studies have suggested that exosomes can serve as a new kind of vaccine with promising therapeutic effects in cancer immunotherapy. Exosomes derived from DC pulsed with tumor antigen peptide elicit potent tumor-specific immune responses. Exosomes derived from tumor cells are also a source of shared tumor rejection antigens for CTL cross-priming, andDCs loaded with tumor-derived exosomes induce tumor antigen-specific CTL in vitro and CD8~+ T-cell-dependent cross-protection against different poorly immunogenic tumors in vivo. In combination with proper adjuvants, exosomes-based cancer vaccines can enhance the host immune responses against tumors. For example, exosomes admixed with CpG oligonucleotides are efficient in prophylactic and therape...
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