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Objective:To investigate whether the susceptibility of human colon adenocarcinoma cell SW1116 to lymphokine-activated killer cell (LAK)-mediated lysis could be enhanced by low concentration of sodium butyrate, and the possible involvement of intercellular surface adhesion molecule-1 (ICAM-1) and carcinoembryonic antigen (CEA). Methods:Standard MTT assay was used to evaluate the cytotoxic activity of LAK cells to SW1116 cells, flow cytometric and immunofluorescent techniques were used to determine the expression of ICAM-1 and CEA on tumor cells. Results:Treatment of SW1116 with sodium butyrate leads to an increased resistance to LAK-mediated lysis, accompanied by downregulation of ICAM-1 expression and upregulation of CEA expression. Conclusion: Sodium butyrate inhibits rather than enhance LAK activity against SW1116, probably by changing the expression of ICAM-1 and CEA on target cells, which impair the adherence of effector on target cells.
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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.
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The peripheral blood lymphocytes (PBLs) from 111 cancer patients were isolated and cultured respectively for 23 - 27 days in the medium mainly conditioned by IL-2 and PHA. With ~(125) I-UdR release method, sampling in random way, we examed the cytotoxicities of PBLs and lymphokine-activated-killer (LAK) cells in different culture periods in vitro. The statistic analysis on sufficient data gave the following results: 1. The cytotoxicity against K562 cells increased from 34.78 ?25% of the PBLs to 68.04 ?17.3% of the cells cultured for 8-13 days, afterward, kept about 70% to 23 - 27 days. The constitutional proportion patterns showed that the freshly isolated samples dispersed at a wide range of cytotoxicities (10 - 90%), and that most of the cultured samples ( ~ 85%) concentrated on the range of higher cytotoxicities (50 ~ 95% ) after 8-13 days. 2. The cytotoxicity against Raji cells rose from 8.9 ?8% of the fresh PBLs to 42.1 ?22% of the LAK cells at 8 - 13 days, and maintained about 35% in the following periods. The constitutional proportion patterns of the cytotoxicity against Raji illustrated that all the fresh PBL samples were below 25% of cytotoxicity, and that during the culture, one part of the samples ( ~ 30%) acquired the higher cytotoxicities (50 -90% ), but the other part of the samples ( - 40%) remained at lower cytotoxicities (below 35% ) . The mechanisms behind these phenomena are worth further investigating.
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In order to study the enhancement of immune functions and autologous tumor-killing (ATX) activity by kappa-selenocarrageenan (KSC) in mice bearing sarcoma 180, the effects of KSC and/or Cyclophosphamide (Cy) on natural killer(NK) activity, lymphokine activated killer(LAK) activity, the production of interleukin-2 (IL-2), ATK activity and the growth of sarcoma 180 (S180) were observed. The results showed that KSC promoted NK activity, LAK activity and ATK activity in vivo, increased IL-2 production at 40mg/kg ?d x 9d. It also enhanced the antitumor action of Cy (20mg/kg?d x 9d) and offsetted the inhibition of Cy on immunocompetent cells. The ATK activity in splenocytes of SI80-bearing mice could be induced and augmented by recombinant interleukin-2 (rIL-2) in vitro. In conclution, KSC had a up-regulating effect on immune functions and ATK activity in tumor-bearing mice, therefore, can be used as a biological response modifier (BRM) in cancer biotherapy.
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Using ovarian cancer cell lines, we studied relationship between C-erbB2 expression and lysis activity of lymphokine-activated killer cells (LAK) and in vitro regulation by ?-interferon (IFN-?). The results showed that C-erbB2 overexpression was associated with resistance to lysis activity of LAK in ovarian cancer; IFN-? could reduce the overexpression of C-erbB2 and increase lysis activity of LAK on ovarian cancer cells in which C-erbB2 were overexpressed.
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In this study, we demonstrated that immobilized fibronectin (FN) enhanced LAK activity, and that the enhanced LAK activity was completely abrogated by an anti-VLA-5 monoclonal antibody and RGD peptide. Fresh -spleen cells expressed VLA-4, VLA-6 and vitronectin receptor, whereas VLA-5 was expressed only on the spleen cells activated with IL-2. LAK cells showed increased adhesion to immobilized FN compared with that to control BSA, and the increased adhesion of LAK cells to immobilized FN was inhibited by anti-VLA-5 monoclonal antibody. Conjugate-formation assay showed that the LAK cells cultured on immobilized FN bound to target cells more efficiently than the control LAK cells, and that anti-LFA-1 monoclonal antibody inhibited the LAK-target cell binding. Immobilized type IV collagen and laminin, as well as FN, enhanced LAK activity. All these results suggest that the interaction of inte-grins expressed on LAK cells with extracellular matrix proteins act as co-stimulator for the enhancement of LAK activity , and that anchorage is necessary for full activation of LAK cells.
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TIL were isolated from the resected tumor mass,and lymphocytes were separated from pe-ripheral blood of 12 patients with osteosarcoma.In vitro antitumor activity and spesificity of rIL—2 activated TIL and LAK cells were determined by 4 hour ~(51)Cr releasing assay.Phenotypeanalysis of TIL were carried out in different intervals of incubation.The results revealed thatduring the incubation period from Day 15—Day 20,the difference between average cytolytic ac-tivities of TIL and LAK ceils with K562 and LiBr cells as target cells(E:T ratio 25:1)were in-significant,while that from 7 of those patients with autotumor cells as target cells were signifi-cant.The phenotype analysis showed that the percentage of CD3~+ cells remained constant,whilethat of CD4~+ cells tends to increase,and that of CD8~+cells tends to decrease during the whole in-cubation period.
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We previously demonstrated the cytotoxicity of human LAK cells to solid tumors in vitro. The work we reported here investigated the mechanisms involved in killing of solid tumor cells by LAK cells. It was shown that the cytotoxicity of LAK cells was mediated by some factors secreted by LAK cells and effects of direct contact with targets. Following lysis, the nucli of targets were destroyed and fragments of DNA were released into the medium. The cytotoxicity of LAK cells, under some circumtances, was of a positive correlation to the proliferation of themselves.
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We have investigated, in both cases of normal individuals and tumor- bearing patients, the cytotoxic activity of lymphokine- activated killer (LAK) cells to cultured cell lines or fresh solid tumor cells with a 4- hour chromium 51 (~(51)Cr) - release assay. The LAK cells were generated by incubating peripheral blood mononuclear (PBM) cells in vitro with recombinant interleukin 2 (rIL- 2)or partially purified interleukin2(PPIL- 2). Our results indicated that these two sources of L \K cells were cytotoxic to either K562, NK- sensitive or Daudi, NK resistant tumor cell lines. These two kinds of LAK cells could also kill a broad rang of fresh solid tumor cells, suggesting that these cells be indeed LAK cells. Furthermore, the results demonstreated that some fresh solid tumor cells were resistant to LAK cell killing to some extent as they showed different sensitivities to LAK cytotoxicity.
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It was demonstrated that TILs exhibited higher cytotoxicity to autologous tumor cells than that of LAK cells grown under identical conditions, and TILs had target cell specificity.The cytotoxicity of TILs to other tumor cells was lower than that of LAK cells, and TILs had no cytotoxicity to ConA-induced lymphoblast cells but LAK cells did have some cytotoxicity to the normal cells. The cytotoxicity of TILs to B 16 melanoma cells was reduced by monoclonal antimelanoma antibodies (M2590 and M562) which can block the activity of antimelanoma CTL, suggesting TILs contained high level of CTL activity. TILs were found to be more effective in their therapeutic potency in vivo on a percell basis than were LAK cells. These results indicate that TILs are more suitable to the adoptive immunotherapy of turn or as effector cells than LAK cells.
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24 patients with chronic hepatitis B were treated with interleukin-2 activated human peripheral blood lymphocytes (IAPBL). 23 patients served as control. The results showed that HBeAg disappeared in 54.2% of IAPBL group, in comparison with 17.4% of the controls (P
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We have shown that tumor-infiltrating lymphocyte (TIL) cultured in interleukin-2 (IL-2) acquired a potent antitumor activity and had target cell specificity.TIL exhibited higher cytotoxicity to autologous tumor cells than that of LAK cells grown under identical conditions (P0.05), so that it is possible to treat recurrent and unresectable tumor using TIL periodically.