Direct gene transfer offers the potential to introduce DNA encoding therapeutic proteins treat human disease. Previously, in humans has been achieved by a cell-mediated ex vivo approach which cells from blood or tissue of patients are genetically modified laboratory and subsequently returned patient. To determine feasibility safety directly transferring genes into humans, clinical study was performed. The foreign major histocompatibility complex protein, HLA-B7, introduced HLA-B7-negative...

We showed previously that adoptive immunotherapy with the combination of LAK cells and recombinant IL 2 (RIL 2) can markedly reduce pulmonary micrometastases from multiple sarcomas established 3 days after i.v. injection syngeneic tumor in C57BL/6 mice. In this report, we analyzed factors required for successful therapy. Titration analysis vivo revealed an inverse relationship between number metastases remaining treatment both amount RIL administered. Fresh or unstimulated splenocytes had no...

Lymph nodes (LN) draining progressively growing tumors contain tumor-sensitized but not fully functional preeffector lymphocytes. These cells could acquire therapeutic efficacy and be expanded upon sequential culture with anti-CD3 mAb for 2 days followed by incubation in IL-2 3 days. Using the weakly immunogenic MCA 106 205 murine sarcomas, we have further defined conditions of this anti-CD3/IL-2 activation which differentiated into immune effector cells. In vitro expansion required...

The systemic administration of high-dose recombinant IL 2 mediated significant reductions established 3-day pulmonary micrometastases from both weakly immunogenic and nonimmunogenic sarcomas. However, when treatment with was delayed for 10 days after the injection tumor cells in an attempt to treat grossly visible macrometastases, only those sarcomas remained susceptible. Established 10-day nodules became refractory therapy. We utilized selective depletion lymphocyte subsets vivo by specific...

PURPOSE In preclinical studies, we have reported the ability to induce immune T cells in lymph nodes (LN) primed by vivo vaccination with tumor admixed a bacterial adjuvant. These LN can be activated and expanded ex for successful immunotherapy of established tumors. We applied these methods generate vaccine-primed patients advanced melanoma renal cell cancer (RCC) therapy. MATERIALS AND METHODS Irradiated autologous bacille Calmette-Guérin (BCG) were used vaccinate patients. Seven days...

To determine the feasibility, toxicity, and potential therapeutic benefits of systemic adoptive immunotherapy, 10 patients with progressive primary or recurrent malignant glioma received this treatment. Adoptive transfer immune T lymphocytes, is capable mediating regression experimental brain tumors in animal models. In models, lymph nodes (LNs) that drain tumor vaccine site are a rich source tumor-immune cells.In clinical study, were inoculated intradermally irradiated autologous cells...

Abstract Systemic transfer of sensitized lymphocytes can effectively mediate the regression established tumors. However, virtually all prior experimental applications this approach have utilized from animals that been immunized to reject tumor challenge. A similar source cells is not available in human. With use a weakly immunogenic murine tumor, MCA 105, we demonstrate here following vitro sensitization (IVS) with viable and interleukin 2, nontherapeutic lymphoid mice bearing progressively...

Our previous studies demonstrated that the incubation of human peripheral blood lymphocytes or murine splenocytes in recombinant interleukin 2 (RIL 2) resulted generation lymphokine-activated killer (LAK) cells capable lysing a broad spectrum fresh tumors short-term chromium-release assays. Moreover, injections LAK plus RIL were highly effective eliminating established 3 day metastases lung and liver (1-3). We have examined several parameters to define whether not cytolytic activity as...

We have previously established an in vitro sensitization (IVS) procedure with which lymphocytes from tumor-bearing mice could be expanded and sensitized to acquire antitumor reactivity capable of mediating the regression pulmonary metastases weakly immunogenic MCA 105 murine sarcoma. Culture conditions required for optimal generation therapeutic effector cells were evaluated current study. Generation by IVS stimulation intact tumor cells. Tumor killed heat or disrupted sonication...

Abstract We have investigated the efficacy and immunologic characteristics of immune effector cells generated from cultures containing large numbers viable tumor interleukin 2 (IL 2) in adoptive immunotherapy experimentally induced pulmonary metastases newly developed, weakly immunogenic MCA 105 sarcoma mice. The current culture conditions allowed increases either normal or spleen up to 94-fold 15 days. vitro expanded displayed nonspecific cytotoxicity against several syngeneic targets....

Abstract The adoptive transfer of sensitized lymphocytes is an effective means to mediate the regression established tumors. However, successful therapy can only be demonstrated in animal models where tumors are intrinsically immunogenic, capable eliciting systemic immunity. To explore potential this therapeutic approach less immunogenicity, we have selected and used a murine tumor, MCA 102, for current study because all attempts immunize syngeneic mice failed. We report here that...

A cluster-sampling, cross-sectional study was conducted for assessing the prevalence of Cryptosporidium infection in children less than 16 years age from three villages, Dondian, Linshan, and Fuziyin, rural Anhui eastern China. Among 320 apparently healthy 10 Dondian who had stool specimens collected, cryptosporidial oocysts were found stools no positive 239 studied Linshan. In addition, a total 610 serum samples these villages tested specific IgG antibody to with an enzyme-linked...

Abstract In animal studies, lymph nodes (LN) draining progressive tumors contain immunologically sensitized but functionally deficient T cells. These preeffector cells can differentiate into mature effector on stimulation in vitro with anti-CD3 and IL-2. However, react all the activated cell population expressed a broad normal distribution of V beta phenotypes. this study, we examined feasibility using bacterial superantigens to stimulate tumor-draining LN Because their TCR restriction,...

Abstract A newly induced syngeneic transplantable sarcoma, MCA 105, was used for studies of the biologic characteristics fresh noncultured and secondarily in vitro sensitized (IVS) cells with antitumor reactivity. Fresh spleen harvested from mice immunized to 105 tumor by a mixture viable Corynebacterium parvum exhibited no detectable cytotoxic activity targets 4-hr chromium-release assay, adoptive transfer these mediated specific regression established tumors. Phenotypic analysis fresh,...

The successful adoptive immunotherapy of the syngeneic Friend virus-induced murine leukemia FBL-3 was mediated by a proliferative MHC-restricted, tumor-specific CTL clone in combination with recombinant human IL 2. This previously shown to express L3T4-, Lyt-1+, Lyt-2+ surface phenotype. Activation for 48 hr vitro irradiated tumor cells induced expression 2 receptors and markedly increased clonal proliferation response Intravenous injection X 10(7) vitro-activated cloned cells, followed 6...

We have previously demonstrated that following the adoptive transfer of immune cells, regression established pulmonary metastases from a weakly immunogenic sarcoma, MCA 105, required collaboration two T cell subsets. In this study, we found critical role played by L3T4+ cells was to provide helper function since tumor proceeded in absence if exogenous interleukin 2 (IL-2) administered. To extend these observations, analyzed events leading induction and generation Lyt-2+ after immunization...

The adoptive transfer of specifically sensitized T lymphocytes can effectively mediate the regression established local and metastatic tumors. Previous experiments using weakly immunogenic MCA 105 sarcoma indicated that cellular interactions between transferred L3T4+ helper Lyt-2+ cytotoxic immune cells were necessary for mediating tumor regression. In this study, kinetics T-T cell analyzed by in vivo depletion subsets with mAb. anti-tumor efficacy was abrogated administration either L3T4 or...

Lymphokine activated killer cell is a newly described lytic system against variety of solid tumours and distinct in several respects from the classic cytolytic T natural systems. This study was conducted to evaluate activity lymphokine cells fresh autologous allogeneic, as well cultured hepatocellular carcinoma cells. generated by incubating peripheral blood mononuclear with various concentrations recombinant IL-2 (rIL-2, Cetus, USA) for periods time. A four hour 51Cr release assay used...