Alteration of a membrane associated marker in transplantable rat pancreatic acinar cell carcinoma

A monoclonal murine IgG has been developed which detects a cellularand intracytoplasmic membrane marker expressed only in the ratpancreatic acinar cell. Membrane aberrations in chemically inducedtransplantable rat pancreas acinar cell adenoma and carcinomawere examined using this IgG. The presence of this membranemarker was assessed by indirect immunofluorescence using paraffinsections of normal pancreas, acinar cell adenoma and transplantedtumors from rats and nude mice. The intracytoplasmic membraneof cells in acinar cell adenoma revealed a much higher intensityof fluorescence compared with normal acinar cells. In contrastthere was an almost complete absence of fluorescent stainingof the intracytoplasmic membranes of acinar cell carcinoma whiletheir cell membranes showed an intensity of fluorescence farexceeding that of normal acinar cells. These findings suggesta defect in the dynamics of membrane-associated antigen(s) inthese cancer cells.     

LD Typing and the Lack of Involvement of SD Antigens in the Priming Process

Peripheral blood lymphocytes with known HLA-SD were typed for LD determinants using a panel of primed cells prepared from SD identical lymphocytes. Then these lymphocytes (with known SD and LD) were primed by x-irradiated cells from the same SD and LD group and their secondary reactions were evaluated. Disparity in SD antigens of responder and stimulator cells did not produce primed cells and lymphocytes were primed only for LD differences. This finding allows LD typing using primed cells from a panel of randomly selected lymphocytes regardless of their HLA-SD.     

Autologous adjuvant linked fibroblasts induce anti-glioma immunity: implications for development of a glioma vaccine

Summary Objectives: Adjuvant-linked vaccines have been shown to induce anti-tumor immunity in patients with a variety of solid tumors. In this study we describe anin vitro model of active immunotherapy using autologous fibroblasts as immunogen. Correlative results from glioma patients immunized with autologous fibroblasts are also described. Methods: Peripheral blood lymphocytes (PBLs) from normal subjects were immunizedin vitro against autologous skin fibroblasts coupled to the adjuvant muramyl dipeptide. The lymphocytes developed cell-mediated cytotoxicity that was measured with a short-term chromium release assay. Results ofin vitro experiments were compared to data derived from glioma patients immunized with subcutaneous injection of an autologous adjuvantlinked fibroblast vaccine. Glioma target cells and fibroblast immunogens were derived from early passage primary tissue culture. Results: A comparison of autologous vs. homologous immunogen indicated that major histocompatibility complex matching was required at the sensitization stage of immunity (17.2±3.4% specific lysis vs. 0.4±3.1%,P<0.01). Pre-treatment of fibroblast immunogen cells with interferon gamma (IFN-γ) was found to significantly increase immunity (42.2±10.0%,P<0.01), as did IFN-γ pre-treatment of tumor target cells (35.8±9.0%,P<0.01). The positive effect of IFN-γ was diminished by treatment of cells with IFN-α. Thesein vitro results correlated well within vivo data derived from glioma patients immunized with an autologous adjuvant-linked fibroblast vaccine. PBLs from patients developed direct cell-mediated cytotoxicity against autologous tumor cells. Lysis of tumor targets afterin vivo immunization increased over a three-week interval (from 1.2 ± 3.0% to 21.0 ± 3.4%,P < 0.01) while lysis of a non-MHC matched control cell line remained essentially unchanged. Conclusions: Specific lysis of glioma targetsin vitro was achieved afterin vivo sensitization with autologous adjuvant-linked fibroblasts. Collectively, the data indicate that biochemically modified autologous cells can stimulate anti-glioma immunity in humans. The degree of specific immunity seen in our patients compares favorably with other published series using glioma cells as an antigenic source. Accordingly, fibroblasts may represent a practical alternative to glioma cells for vaccine construction.