Augmentation of in vitro lymphocyte blastogenesis and cytotoxicity responses by tumor cells modified with dodecanoyl cytochrome C.
In a model testing the immune responsiveness of allogeneic lymphocytes against the human cervical cancer cell line SW756, tumor cells coupled to dodecanoyl cytochrome C (D-cyt C) demonstrated augmented immunogenicity. The coupling was noncovalent; the D-cyt C spontaneously associated with the SW756 cells during mixing. Augmented immunogenicity was shown in both in vitro blastogenesis and cytotoxicity assays. The extent of cell-associated D-cyt C, which influenced the in vitro responsiveness, was easily controlled. Increased lipoprotein concentrations and increased lipid substitution of the cyt Cs led to greater cell uptake. Under the maximum conditions, 60-80 micrograms D-cyt C were bound/10(7) SW756 cells. In the blastogenesis assay, augmented immunogenicity was observed on days 3 and 4 after cocultivation of the allogeneic lymphocytes with the modified SW756 cells. When cells modified by the optimal D-cyt C preparations (as determined in the blastogenesis assay) were tested in the cytotoxicity assay, augmented responses were observed across a range of lymphocyte:tumor cell ratios. Our results demonstrate that the modification of SW756 cells with D-cyt C can augment the immune responses detected in in vitro assays.
D000268:Adhesiveness; D000276:Adjuvants, Immunologic / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D003574:Cytochrome c Group / Q000031:analogs & derivatives* / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D045304:Cytochromes c; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000378:metabolism
D000276:Adjuvants, Immunologic; D003574:Cytochrome c Group; C044603:dodecanoyl cytochrome C; D045304:Cytochromes c