ABSTRACT
Brucellosis has become a global zoonotic disease, seriously endangering the health of people all over the world. Vaccination is an effective strategy for protection against Brucella infection in livestock in developed countries. However, current vaccines are pathogenic to humans and pregnant animals, which limits their use. Therefore, it is very important to improve the safety and immune protection of Brucella vaccine. In this study, different bioinformatics approaches were carried out to predict the physicochemical properties, T/B epitope, and tertiary structure of Omp2b and Omp31. Then, these two proteins were sequentially linked, and the Cytotoxic T lymphocyte associated antigen-4 (CTLA-4) variable region was fused to the N-terminal of the epitope sequence. In addition, molecular docking was performed to show that the structure of the fusion protein vaccine had strong affinity with B7 (B7-1, B7-2). This study showed that the designed vaccine containing CTLA-4 had high potency against Brucella, which could provide a reference for the future development of efficient brucellosis vaccines.
ABSTRACT
A novel approach of vaccination against cancer is to exploit dendritic cells (DC) as the best antigen presenting cells (APC) and actively immunize cancer patients with a sample of autologous or allogeneic DC primed with tumor antigens. DC vaccination is still at its early stage, however, valuable proofs of concept have been obtained with respect to the capacity of DC to expand cancer directed immune responses. The methods for preparing DC are being improved continuously, and there are many opportunities to improve efficacy at the level of DC biology. An increased number of clinical studies will drive the development of this new area. This paper reviews the production of dendritic cell tumor vaccines and their use in clinical trials, as well as emphasizes some unresolved questions in this immunotherapy.
ABSTRACT
Objective:To investigate the effect of flt-3 ligand on the preparation of the fusional vaccine with dendritic cells and colorectal cancer cells,and the anti-tumor immunological reaction of the vaccine. Methods: ①In the presence of Flt-3 ligand、GM-CSF、IL-4 and TNF,the maturation of dendritic cells was made from peripheral blood;The preparation of the fusional vaccine was made in the presence of PEG. ②The biological characteristics of fusion cells,including their morphological specialties, the expression of cell surface phenotypes, their growth curves, inducing specific cytotoxic T lymphocyte(CTL), their possibility to proliferate into a new carcinoma in nude mice etc, were tested to verify their safety when used as anti-tumor immune reactions. Results: ①Flt-3 ligand can stimulate the full maturation of dendritic cells. Dendritic cells and Lovo cells could be fused by PEG. ②The fusion cells exhibited typical biological characteristics. They could not proliferate into new carcinomas in nude mice, and can inhibit the proliferation of Lovo cells efficiently. Conclusion: Flt-3 ligand can enhance the maturation of dendritic cell. The fused cells had poor proliferation abilities and could not proliferate into new carcinomas in immunodeficient animals. The fusion vaccine could induce specific cytotoxic T lymphocytes in vitro and was safe as a vaccine.
ABSTRACT
Objective To study on the cytotoxic effects in vivo and in vitro of the T lymphocytes which were activated by the DC-gastric cancer cell fusion vaccines. Methods The mononuclear cells were separated from the peripheral blood of gastric cancer patients and co-cultured with granulocyte-macrophage colony stimulating factors, interleukin-4 and tumor necrosis factor-? to generate mature dendritic cells. The human gastric cancer SGC7901 cells and the dendritic cells were fusioned by using polyethylene glycol, and the pure fusion cells were screened out by culturing with HAT and HT selective culture systems. The mixture of SGC7901 and DC without fusion and the T lymphocytes served as controls. The ability of fusion cells activated by T lymphocytes to kill SGC7901 gastric cancer cells was investigated by MTT in vitro. The anti-tumor effects were evalutated by detecting the growth of the new planted tumors in the nude mice, the apoptosis and proliferation of the planted cancer cells, the pathological changes of the tumor tissues and the prohibitive rate for planted tumors before and after the application of the fusion cell vaccine. Results The mature dendritic cells were obtained from peripheral blood mononuclear cells of gastric cancer patients successfully. Dendritic cells and SGC7901 cells were fusioned and the pure fusion cells were got. Fusion vaccine could induce strong anti-tumor biological effects in vivo and in vitro: Tumor growth was remarkably inhibited and the tumor size in mice receiving fusion cells was (1.298?0.021) cm 3, smaller than that in mice receiving T lymphocytes as treatment (P
ABSTRACT
Objective To obtain SGC7901 gastric cancer cell-dendritic cell fusion vaccines by cell fusion technology. The phenotype changes of the fusion cells were detected to provide experimental data for the following research work. Methods The SGC7901 gastric cancer cells and dendritic cells were induced to be fused by PEG and the pure fusion cells were obtained by selective culture with the HAT/HT culture system. The phenotype changes of the fusion cells were detected by flow cytometer. Results The fusion cells had special morphologic characteristic and the phenotypes of the fusion cells were remarkably higher than the parental dendritic cells. Conclusion The SGC7901 gastric cancer cell-dendritic cell fusion cells kept special morphologic characteristic and their phenotypes were significantly higher than the parental dendritic cells, which may be the cellular base for their stronger biological effects.