ABSTRACT
The authors report the results of a phase I clinical study using semiallogeneic cancer vaccines formulated with granulocyte-macrophage colony-stimulating factor (GM-CSF) to treat patients with metastatic adenocarcinomas of the gastrointestinal tract. A specially engineered cell line, FO1-12, was used to generate semiallogeneic hybrids by fusion with patient-derived tumor cells; the hybrids express HLA class I and II haplotypes derived from both parental cells. For treatment, the vaccine was mixed with GM-CSF, irradiated, and injected intradermally into patients at weekly or biweekly intervals. Vaccinations were associated with minimal or no toxicity and showed that semiallogeneic hybrids formulated with GM-CSF can induce a specific antitumor immune response in some patients, as measured by a delayed-type hypersensitivity response to autologous tumor cells. Because of the simplicity, feasibility, and flexibility of this immunotherapeutic approach, semiallogeneic hybrid vaccines have the potential to be used in the treatment of virtually any type of cancer.
Subject(s)
Adenocarcinoma/secondary , Adenocarcinoma/therapy , Cancer Vaccines/therapeutic use , Gastrointestinal Neoplasms/therapy , Granulocyte-Macrophage Colony-Stimulating Factor/therapeutic use , Adenocarcinoma/immunology , Adult , Aged , Aged, 80 and over , Cancer Vaccines/adverse effects , Cancer Vaccines/genetics , Female , Gastrointestinal Neoplasms/immunology , Granulocyte-Macrophage Colony-Stimulating Factor/adverse effects , Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , Humans , Hybrid Cells/metabolism , Hybrid Cells/transplantation , Immunotherapy, Adoptive/methods , Male , Middle Aged , Pilot Projects , Tumor Cells, Cultured/metabolism , Tumor Cells, Cultured/transplantation , Vaccines, Synthetic/adverse effects , Vaccines, Synthetic/genetics , Vaccines, Synthetic/therapeutic useABSTRACT
Histone mRNAs at different stages of development were purified by hybridization with the cloned homologous histone genes. The electrophoretic patterns of oocytes, 2-4 blastomeres, 64 cells and morula histone mRNAs was found to be identical, whereas the electrophoretic pattern of mesenchyme blastula histone mRNA was markedly different. The cloned histone DNA of P.lividus was hybridized with the RNA of each stage. The Tm was 74 degrees C in all cases except for the mesenchyme histone mRNAs whose Tm was 59 degrees C, thus suggesting that at least two different clusters of histone genes are active in the course of the sea urchin development.
Subject(s)
Genes , Histones/biosynthesis , Protein Biosynthesis , RNA, Messenger/metabolism , Sea Urchins/metabolism , Transcription, Genetic , Animals , Embryo, Nonmammalian/metabolism , Nucleic Acid Denaturation , Nucleic Acid Hybridization , RNA, Messenger/isolation & purificationABSTRACT
It is shown that the RNA of unfertilized sea urchin eggs is active in stimulating protein synthesis in a wheat germ cell free system. This activity is not lowered by conditions that inhibit the methylation processes but is inhibited by a treatment that damages the "cap", A difference in activity in a wheat germ cell free system between the RNA of unfertilized eggs and the RNA from early embryos is described.
