ABSTRACT
@#[Abstract] T cell receptors (TCR) are specifically expressed on T cell surface, which can recognize different tumor antigens to kill and scavenge cancerous cells. TCR-engineered T cells (TCR-T) therapy is to harbor TCR specific to tumor cells and modify the T cells with genetic engineering techniques to achieve the purpose of treating tumors after transfusion. Despite some achievements in TCR-T therapy, there are still some problems, such as treatment toxicity, limited T cell infiltration and antigen-specific deficiency and so on. So, the safety and effectiveness of TCR-T therapy need to be constantly optimized. Therefore，this paper summarizes the research status of TCR-T therapy for solid tumors in domestic and overseas, as well as the existing problems and countermeasures.
ABSTRACT
Objective To observe the clinical efficacy of autologous dendritic cells (DCs) vaccine combined with cytokine-induced killer (CIK) cells for treatment of patients with biliary tract cancer. Methods Peripheral blood mononuclear cells (PBMCs) were collected from the patients with biliary tract cancer and were stimulated with multiple tumor-associated antigens (TAA) for amplification and culture. Mature DCs were harvested and made into vaccine for intradermal administration, and at the same time the patients were given autologous CIK cells via vein transfusion. The clinical efficacy, immune function, side effect, and overall survival of 85 patients with biliary tract cancer were observed before and after treatment. Results The clinical symptoms were improved significantly in the 85 patients after autologous DC-CIK therapy (P +, CD3+CD4+, CD3+CD8+, CD3+CD56+ and CD4+/CD8+ ratio were elevated in the lymhocyte subpopulation, but the regulatory T cells were reduced (P <0.05). At the end of the follow-up, 58 patients died, 2 patients were lost in follow-up, and 25 patients survived, with the median overall survival time being 16.5 months (95%CI: 12.1-20.9 months). Conclusion Autologous DC-CIK therapy is a safe and effective treatment for patients with biliary tract cancer, with less side effect, but the relevant conclusion still needs to be confirmed by larger sample randomized controlled studies.
ABSTRACT
Objective To study proliferation,secreted cytokines,immune phenotypes and cytotoxicity on Raji cells by cytokine induced killer (CIK) cells co-cultured with dendritic cells (DC).Methods The mononuclear cells from peripheral blood of healthy individuals were extracted,then cultured the cells under 5 ％ CO2 at 37 ℃ for 2 hours.DC were induced from suspended cells,and CIK cells were from adherent cells.After 9 days of nurturing,two types of cells were mixed.CIK cells were cultured alone as the control.The cytotoxic activity of CIK and DC-CIK cells were detected by MTT assay.The morphologies,proliferation,secreted cytokines,and immune phenotypes of the two cells in day 0,3,6,9,12,15 in culture were monitored.Results In day 12 in culture,comparing with CIK cells,DC-CIK cells significantly enhanced the proliferation rate [(42.44±2.68) fold vs (30.01±2.05) fold] (t =11.64,P ＜ 0.05) and had increased IL-2,IFN-γ,IL-12 and TNF-α secretion [(124.34±12.57) ng/L vs (56.32±6.58) ng/L,(496.60±95.32) ng/L vs (247.80± 69.45) ng/L,(84.92±6.07) ng/L vs (24.18±3.31) ng/L,(380.6±45.95) ng/L vs (196.61±24.19) ng/L] (t =15.16,P ＜ 0.05; t =6.67,P ＜ 0.05; t =27.78,P ＜ 0.05; t =11.20,P ＜ 0.05),and there were more CD3+ CD8+ cells and CD3+ CD56+ cells in the co-culture [(71.79±1.73) ％ vs (60.37±3.24) ％,(48.54±3.30) ％ vs (33.07±2.22) ％](t =9.83,P ＜ 0.05; t =12.30,P ＜ 0.05),and DC-CIK cells had a significandy increased cytotoxicity on Raji cells in vitro at the same ratio of effector cells to target cells.Conclusion CIK cells have higher proliferation rate and cytotoxicity against Raji cells when co-cultured with DC.
ABSTRACT
Objective To evaluate the clinical effects of cytokine-induced killer (CIK) cells combined with chemotherapy on the treatment of patients with advanced colorectal cancer.Methods CIK cells were prepared from 50 ml peripheral blood mononuclear cells by stimulated with IL-2,IFN-γ,anti-CD3 monoclone antibody,IL-1 for 8 d.The clinical effects and survival rate were compared between CIK cells combined with chemotherapy group and the chemotherapy group (50 patients with advanced colorectal cancer for each).T cells and NK cells of patients were tested by FCM before and after CIK cells treatment.The improvement of quality of life and toxicity of this therapy were observed.Results The percentages of CD3+,CD4+,CD8+ T cells and NK cells were (54.779±14.228) ％,(30.821±11.554) ％,(16.676±6.256) ％,(18.705±9.347) ％ before CIK cells transfusion.After transfusion,the percentages were (65.236±14.901) ％,(37.292±8.880) ％,(25.229±6.711) ％,(22.950±8.933) ％,respectively.The percentages were expanded greatly (P ＜ 0.05).The patients quality of life were improved clearly with lower toxicity.The DCR of CIK cells combined with chemotherapy group (64 ％,32/50) was higher than the chemotherapy group (40 ％,20/50) (P ＜ 0.05).The survival rate between two groups had no statistical significance (P ＞ 0.05).Conclusion Administration of CIK cells combined with chemotherapy can enhance immune function in patients with advanced colorectal cancer and improve their quality of life,and get good clinical efficacy.
ABSTRACT
Adoptive cellular immunotherapy is a novel treatment that uses immunological cells with antitumor activity,expanded in vitro and infused into the patient with tumor.The activated immunological cells mediate direct or indirect anti-tumor response via tumor ceUs killing or lysis.This article reviews some novel advances of immunological cells used in adoptive cellular immunotherapy for leukemia,such as NK cell,artificial antigen-presenting ceils,leukemia-derived dendritic cells,CD4+T ceHs,Th17 cells and mixed immunological cells.
ABSTRACT
OBJECTIVE: The objective of this study was to establish a clinically applicable culture system by investigating the use of autologous cord blood plasma (ACBP) instead of fetal bovine serum (FBS) for the ex vivo expansion of umbilical cord blood (UCB) T-lymphocytes. METHODS: Fresh UCB mononuclear cell (MNC) fractions were isolated by Ficoll-Hypaque density centrifugation. The nonadherent MNC fractions were then cultured with the anti-CD3 antibody 5 microgram/mL plus IL-2 175 U/mL in the presence of 10% FBS, 10% ACBP or homologous cord blood plasma (HCBP). On day 8, proliferation rate, cell surface markers, cytotoxic assay of UCB T-lymphocytes according to the medium supplemented with FBS, ACBP or HCBP were evaluated. RESULTS: Proliferation studies demonstrated a significant increase in the proliferative ability of UCB T-lymphocytes incubated in anti- CD3 and IL-2 irrespective of the medium supplemented with FBS or ACBP. In the FBS supplemented medium, expressions of the activated T-lymphocytes were increased significantly after culture: CD3+CD8+, CD3+CD25+, CD3+CD38+, and CD45RO+ (p<0.05). Also in the ACBP supplemented medium, expressions of the activated T-lymphocytes were increased significantly after culture: CD3+ CD8+, CD3+CD25+, and CD45RO+ (p<0.05). In the HCBP supplemented medium, expressions of the activated T-lymphocytes were increased significantly after culture as in the ACBP: CD3+CD8+, CD3+CD25+, and CD45RO+ (p<0.05). Of the activated T-lymphocytes, increase of cytotoxic CD3+CD8+ cells increased significantly in the ACBP and HCBP groups compared to FBS group (p<0.05). CONCLUSION: These findings support the feasibility of ex vivo expansion of umbilical cord blood T-lymphocytes in the medium supplemented with autologous cord blood plasma, instead of fetal bovine serum, for future adoptive cellular immunotherapy.
Subject(s)
Centrifugation , Fetal Blood , Immunotherapy, Adoptive , Interleukin-2 , Plasma , T-Lymphocytes , Umbilical CordABSTRACT
Objective To investigate the feasibility of lymphokine activated killer(LAK) cells induced from cord blood used as adoptive cellular immunotherapy for human cancer.Methods Mononuclear cells were separated from umbilical blood(UBMC) by Ficoll,and stimulated by IL-2.The phenotypes(CD3/ CD4/ CD8) of the mononuclear cells were assayed by Flow cytometry,and their lethal activity on K562 or SKOV6 assayed by MTT colometric.The peripheral blood mononuclear cells were used as the control.Results The in vitro anti-tumor effect of LAK from cord blood was significant.Conclusion LAK from cord blood can be a source of adoptive cellular immunotherapy in the treatment of human cancer.
ABSTRACT
Objective:To investigate the inhibitory effects of cytokine induced-killer(CIK) cells combined with docetaxel(DTX) on the expansion of lung adenocarcinoma cell line SPC-A1/DTX in vitro and in vivo.Methods:Peripheral blood mononuclear cells(PBMC) from healthy donors were incubated in vitro to induce CIK cells in the presence of interferon-gamma(IFN-?),IL-2 and anti-CD3 monoclonal antibody.MTT assay was employed to evaluate the cytotoxic activity of DTX,CIK cells and their combination against SPC-A1/DTX cells in vitro.SPC-A1/DTX lung adenocarcinoma cells were injected subcutaneously into nude mice.On the 14 th day,normal saline(control group),docetaxel(DTX 1 mg/kg in 0.2 ml,DTX group),CIK cells(1?107,CIK group),and CIK cells combined with docetaxel(CIK+DTX group) were administered intraperitoneally respectively.All the nude mice were sacrificed at day 15 after treatment and the tumor were weighted out.Results:MTT assay showed that the IC50 to docetaxel in SPC-A1/DTX cells was 110.5 ?g/ml and 8.5 ?g/ml in wild SPC-A1 cells.CIK cells possessed a higher anti-tumor cytotoxic activity in SPC-A1/DTX cells in vitro than in wild SPC-A1 cells(P
ABSTRACT
Using a syngeneic transplantable leukemia model of 615 inbred mice, named L615, we (1) compared the adoptive immunoprophylactic(AIP) effects of spleen cells from various normal dornor mice with different genetic background and from different immune-deficient mice;(2) studied the adoptive immunotherapeutic (AIT) and adoptive chemo-immunotherapeutic(ACIT) effects of immune spleen cells from those survival mice in the AIP groups;(3) analysed the antitumor activities of various murine spleen cells either nonspecifically activated in vitro or specifically induced in vivo and resensitized in vitro by MMC-treated L615 tumor cell vaccine (TCV).Our results might provide some new experimental evidences for clinical application of cancer ACI.