Objective To detect the anti-colon cancer ability of whole cell lysates pulsed dendritic cell (DC) which acts as an adjuvant. Methods Whole cell lysates of LoVo cells were extracted with freeze thawing method, then the monocyte-derived DC were pulsed with this cellular antigen. Subsequently, the capability of antigen pulsed DC to promote T lymphocytes proliferation and the ability of T lymphocytes to kill LoVo cells were detected by 3H-TdR incorporation and lactate dehydrogenase release methods, respectively. Results The whole cell lysates of LoVo cells pulsed DC significantly stimulated T cells proliferation, and the cytotoxicity abilities of primed T cells to kill LoVo cells were also enhanced. Conclusion Tumor cell lysates which act as the cellular antigen to pulse DC can improve the efficacy of anti-cancer immune response， which provides us an experimental evidence for cancer immunotherapy.
Objective To review the advance in the experimental studies and evaluate the potential therapeutic application of the mesenchymal stem cells(MSCs). Methods The related articles published in China and theother countries during the recent years were extensively reviewed and analyzed. Results The MSCs were widely used in the cell-transplantation therapy and the tissue engineering because of their pluripotency of differentiation into various kinds of cells. They were also frequently used in the gene therapy because they could stably express the transfected objective genes. Because of their immunomodulatory function, the MSCs could also be used in the immunotherapy. Conclusion The MSCs are the stem cells, which have characteristics of renewing themselves, having multipotency, and being easy to undergo amplification in vitro.The MSCs are ideal target cells for the cell therapy, tissue engineering, gene therapy, and immunotherapy.
Objective To observe the expression of molecules on surface of dendritic cells (DC) in retinoblastoma (RB) patients, and investigate its relationship with immune function. Methods The peripheral blood of 50 normal subjects (control group) and 18 RB patients (RB group) were collected to proliferate the DC.The mixed lymphocyte reaction was performed on DC of the control and RB group to detect the antigen-presenting ability. The DC of control group was cultured in the supernate of SO-RB50 with the different concentration of 25% (group A), 50% (group B) and 75% (group C). Then the expression of HLA-DR, CD54 and CD80 on surface of DC were detected by flow cytometry (FCM). Results The Results of MLR showed that DC antigen-presenting ability was gradually enhanced with the increase of stimulation of the cell. And the DC antigen-presenting ability of the control group was superior to that of the RB group (P＜0.05). The expression of HLA-DR, CD54 and CD80 on surface of DC in the control group (12.14plusmn;2.52, 34.89plusmn;5.12, 10.93plusmn;3.1) were significantly higher than that in the RB group (7.33plusmn;2.20, 25.28plusmn;4.54, 7.89plusmn;3.75) (t=4.07, 3.96, 2.59; P＜0.05). The expression of HLA-DR, CD54 and CD80 on surface of DC in the group A, B and C (HLA-DR: 9.95plusmn;2.55, 6.48plusmn;1.82, 3.11plusmn;1.47; CD54: 34.75plusmn;4.92, 21.25plusmn;3.44,15.41plusmn;3.52; CD80: 9.15plusmn;2.18,5.05plusmn;2.01,2.90plusmn;1.10) were reduced in varying degrees compared with the control group; and with the increase of the concentration of supernate SO-RB50, the reduction was more evident (F=8.96,13.62, 20.72; P＜0.05). Conclusions The expression of molecules on surface of DC in RB patients is lower than that in the normal subjects. It is closely related to the functional deficiency of DC.
Objectives To evaluate the effect and safety of mycobacterium vaccae in the treatment of recurrent treated pulmonary tuberculosis. Methods We searched PubMed (1997 to 2006), VIP (1997 to 2006), Wanfang database (1997 to 2006), The Cochrane Central Register of Controlled Trials (Issue 4, 2006) and the National Research Register (1996 to 2006). Randomized controlled trials comparing the mycobacterium vaccae immunotherapy group and the control group were included. Two reviewers independently performed data extraction and quality assessment. Data were analyzed using RevMan 4.2.2 software by The Cochrane Collaboration. Results Eleven high quality trials were included. Meta-analyses showed that mycobacterium vaccae immunotherapy plus chemotherapy resulted in higher sputum negative conversion rate (RR=1.36, 95%CI 1.21 to 1.54), higher lesion absorption rate (RR=1.39, 95%CI 1.13 to 1.72), and lower lesion non-absorption rate (RR=0.46, 95%CI 0.36 to 0.60), compared with the control group. These differences were all statistically significant. No serious adverse events were reported. Conclusion As an adjunct to chemotherapy, mycobacterium vaccae is helpful for patients with recurrent treated pulmonary tuberculosis in terms of improving cell-medicated immunity, sputum negative conversion and X-ray manifestation. More high quality studies are needed for further analysis.
ObjectiveTo explore the antitumor effect of tumor vaccine fused from dendritic cells (DC) and Walker-256 cancer cells on implanted liver cancer in rats and the related mechanism of inhibition for tumor angiogenesis. MethodsWalker-256 cancer cells and mature DC were fused by 50% polyethylene glycol method for preparation of DC-Walker-256 fusion vaccines. Implanted liver cancer models were established through operations on healthy male SD rats at the age of 6－8 weeks. All the rats were divided into four groups, and rats in each group were injected subcutanely with fusion vaccine (group), mixed cultured cells (group), simple DC (group), and PBS (blank control group), respectively. On 28 d after making model, the rats were put to death, the tumor was observed and pathological essays were prepared. All rats’ spleens were collected and prepared into lymphocyte to detect antigenic specificity cytotoxic T lymphocyte (CTL) by enzymelinked immunosorbent spot (ELISPOT) method. The expressions of VEGF, ANG-1, ANG-2, and MVD were detected by immunohistochemistry. ResultsThe numbers of rats survived in the fusion vaccine group, mixed culture cells group, simple DC group, and blank control group was 8, 5, 6, and 3, respectively. The rats in the other three groups except for fusion vaccine group were manifested as inaction, anorexia, and gloomy fur in some degree as well as ascites. The tumorigenesis was found in all survival rats except for two in the fusion vaccine group. The weight of liver tumors of rats in the fusion vaccine group 〔(32.4±9.2) g〕 was significantly lighter than that in the mixed culture cells group 〔(67.3±5.1) g, P=0.031〕, simple DC group 〔(75.0±8.3) g, P=0.019〕, and blank control group 〔(86.6±10.5) g, P=0.008〕, respectively. The number of tumorspecific CTL of rats in the fusion vaccine group was also significantly higher than that in the other three groups (P=0.019, P=0.025, and P=0.001, respectively). The MVD of tumor tissue in the fusion vaccine group was (24.12±2.32) vessels/HP, which was significantly lower than that in the mixed culture cells group 〔(40.34±1.29) vessels/HP, P=0.025〕, simple DC group 〔(42.36±3.16) vessels/HP, P=0.035〕, and blank control group 〔(56.48±5.16) vessels/HP, P=0.006〕, respectively. The MVD of tumor tissue in the mixed cultured cells group and simple DC group was similar (P=0.165), however, which was significantly lower than that in the blank control group (P=0.040 and P=0.043). The positive rate of VEGFA protein expression was 23.2% in the fusion vaccine group, which was significantly lower than that in the mixed culture cells group (42.5%, P=0.031), simple DC group (61.3%, P=0.019), and blank control group (89.6%, P=0.003), respectively. The positive rate of VEGF-A protein expression in the mixed cultured cells and simple DC groups was similar (P=0.089), however, which was significantly lower than that in the blank control group (P=0.027 and P=0.038). The positive rate of ANG-1 protein expression in the fusion vaccine group (43.2%) was not different from that in the mixed culture cells group (46.3%, P=0.292), simple DC group (51.3%, P=0.183), or blank control group (49.6%, P=0.179), respectively, and the difference of pairwise comparison in latter three groups was not significant (P=0.242, P=0.347, and P=0.182). The positive rate of ANG2 protein expression was 19.2% in the fusion vaccine group, which was significantly lower than that in the mixed culture cells group (62.3%, P=0.007), simple DC group (67.3%, P=0.005), and blank control group (71.6%, P=0.004), respectively, however, the difference of pairwise comparison in latter three groups was not significant (P=0.634, P=0.483, and P=0.379). ConclusionFused vaccine can induce CD8+ CTL aiming at tumor cells and establish the effective antitumor immunity in vivo and also downregulate the level of VEGF and ANG-2 to suppress tumor angiogenesis and thereby achieve the purpose of curing tumor.
【Abstract】ObjectiveTo generally analyze the current situations and advancement of the study on immunotherapy for colorectal cancer. MethodsThe pertinent published papers about the current situation and research advancement of the immunotherapy of colorectal cancer were retrospectively investigated. And also the immunogenicity and the varying principles of immunoresistance, the functional targets, the practicality, and some other characteristics of different immunotherapy for colorectal cancer were reviewed. ResultsThe main treatments and the research focuses in the immunotherapy of colorectal cancer are initiative nonspecific immunotherapy, adoptive immunotherapy, monoclonal antibody immunotherapy, initiative specific immunotherapy, and targeted therapy. They work by fighting against the cancer itself, cutting off the tumor’s nutrition supply, activating the immune system specifically or breaking the immune tolerance and so on. Though there are still many problems unsolved, immunotherapy has a promising clinical prospect. ConclusionAs a beneficial complement for surgery, chemotherapy and radiotherapy， immunotherapy plays an important auxiliary role in the combined therapy for colorectal cancer.
【Abstract】Objective To explore the effect against gastric cancer induced by Newcastle disease virus modified autologous tumor vaccine （NDV-ATV）pulsed dendritic cells(DCs). Methods The Newcastle disease virus infected the gastric cancer lines (MNK45) and was lost its activity. Peripheral blood mononuclear cell (PBMC) were cultured under condition of recombinant human granulocyte macrophage-colony stimulating factor (1 000 u/ml)+IL-4(1 000 u/ml) + TNF-α(100 ng/ml). The tumor antigen specific cytotoxic T lymphocytes (CTL) was generated from activated autologous T cell by the Newcastle disease virus infected the MNK45 pulsed DC. And Cyto Tox 96TM in vitro assayed the cytotoxicity of CTL to MNK45. Thawed gastric cancer cell antigen were used as control in these experiments. Results The killing rate of MNK45 by antigen specific CTL reached (90.15±9.82)%, which was nearly twice as high as that of control(60.57±5.74)%. The CTL had much higher cytotoxicity to different differentiated type of gastric cancer cells such as MGC803〔(52.23±6.45)% 〕 and SGC7901〔 (61.75±8.84)%〕, as compared with LOVO〔(9.11±3.42)%〕 and HepG2 〔 (8.30±3.12)%〕tumor cells(P＜0.05). Conclusion Efficient and specific of against gastric cancer immunoreaction can be induced in virtue of NDV-ATV pulsed DCs, NDV-ATV loaded DCs might provide a new kind of theraputic means for gastric cancer.
Objective To investigate the effect of B7-1 and IL-12 gene expression on the immunogenicity of hepatocellular carcinoma (HCC) HepG2 cells. Methods Plasmids encoding B7-1 and IL-12 molecules were retrovirally introduced into human HCC cells,empty vector as control. PBLs were cocultured with HepG2/B7-1,HepG2/IL-12 and HepG2/neo cells. Three days later,PBLs were submitted to specific cytotoxicity test and nonspecific cytotoxicity test against K562 cells by MTT assay.Results HLA-Ⅰ molecules on PBLs were detected by FACS.HLA-Ⅰ molecules expressing on PBL cocultured with HepG2/B7-1,HepG2/IL-12 cells were enhanced by 16.95% and 14.71% than those of HepG2/neo group, respectively(Ｐ＜0.05). Specific cytotoxicity against HepG2/B7-1 cells was 12.5% higher than that of against HepG2/neo cell,while no increase in that of against HepG2/IL-12 cells. Cytotoxicities against K562 cells in HepG2/B7-1,HepG2/IL-12 groups were 19.38% and 14.78% higher than those of HepG2/neo group, but no significant difference between the first two groups.Conclusion B7-1 and IL-12 gene transfer could remarkably promote immunogenicity of hepatocellular carcinoma cells and induce b specific and nonspecific immunity against hepatocellular carcinoma in vitro.
ObjectivesTo systematically review the clinical response rate of CD19 chimeric antigen receptor modified-T cells (CD19CART) in the treatment of B cell hematological malignancies.MethodsPubMed, EMbase, CNKI, WanFang Data and VIP databases were searched to collect cohort studies about CD19CART in the treatment of B cell hematological malignancies from 2000 to 2016. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, a single rate meta-analysis was performed by R software and SPSS 16.0 software.ResultsA total of 13 prospective cohort studies were included. The results of single group rate meta-analysis showed that the overall pooled response rate of CD19 CART was 68% (95%CI 0.51 to 0.82). The 6 months and 1-year PFS after CD19 CART infused by Kaplan-Meier were 46% (95%CI 0.35 to 0.56) and 24% (95%CI 0.16 to 0.34), respectively. The median duration was 180 days (95%CI 138 to 222). The COX regression model showed lymphodepletion to be the only influence factor of PFS.ConclusionsCD19 CART has a good clinical response rate in the treatment of B cell hematological malignancies. Lymphodepletion is the only important impact on the response rate and PFS. Due to limited quality and quantity of included studies, more high quality studies are required to verify the above conclusions.
Neuromyelitis optica spectrum disorders (NMOSD) are a group of inflammatory disorders of the central nervous system characterized by episodes of immune-mediated demyelination and axonal damage mainly involving optic nerves and spinal cord. Neuromyelitis optica related optic neuritis (NMO-ON) is a common neuro-ophthalmic disease which often results in permanent blindness. The discovery of aquaporin 4 antibodies confirms that neuromyelitis optica is a distinct disease entity different from multiple sclerosis. In patients with NMO-ON, the correct therapeutic approach has to recognize two distinct clinical situations: treatment of the acute attacks and prevention of the relapses. With the in-depth study of the pathogenesis of NMOSD, new treatments are emerging in different targets of the disease. This review gives an update of latest treatment of NMO-ON, emphasizing both current situation and future immunotherapy strategies.