Most viral vectors are highly immunogenic and are of limthirds of the liver by histological staining. It was found that ited use for somatic gene therapy that requires repetitive the transfection efficiency was not affected by repetitive administrations. We have developed a highly efficient gene transfections. In support of these findings, antibody transduction procedure useful for repetitive transfections response to HVJ-liposome detected in the rat sera was using liposome containing hemagglutinating virus of Japan weak and transient. Furthermore, cytotoxic T lymphocytes (HVJ-liposome). The Escherichia coli -galactosidase (-were not elicited against autologous rat hepatocytes that gal) gene was embodied in HVJ-liposome, and introduced were transfected in vivo using HVJ-liposome. Thus, our directly into the caudal lobe of rat liver that was transiently results demonstrate that the isolation of a target liver from isolated from a systemic circulation. A 116 kDa -gal prosystemic circulation and the direct administration of foreign tein was detected in transfected rat liver tissues by Westgenes using HVJ-liposomes are useful for high gene transern blot analysis and it was expressed in more than twoduction and persistent gene expression in the liver.
Carcinoembryonic antigen (CEA), which is expressed in several cancer types, is a potential target for specific immunotherapy. HLA‐A24 is the most frequent allele among Japanese and is also frequently present in Asians and Caucasians. We tested CEA‐encoded HLA‐A24 binding peptides for their capacity to elicit anti‐tumor cytotoxic T lymphocytes (CTL) in vitro. For this purpose, we used CD8+ T lymphocytes from peripheral blood mononuclear cells (PBMC) of a healthy donor and autologous peptide‐pulsed dendritic cells as antigen‐presenting cells. This approach enabled us to identify 2 peptides, QYSWFVNGTF and TYACFVSNL, which were capable of eliciting CTL lines that lysed tumor cells expressing HLA‐A24 and CEA. The cytotoxicity to tumor cells by the CTL lines was antigen‐specific since it was inhibited by peptide‐pulsed cold target cells as well as by anti‐class I major histocompatibility complex (MHC) and anti‐CD3 monoclonal antibodies (MAbs). The antigen specificity of the 2 CTL lines was examined using several tumor cell lines of various origins and for their peptide‐dose responses. The identification of these novel CEA epitopes for CTL offers the opportunity to design and develop epitope‐based immunotherapeutic approaches for treating HLA‐A24+ patients with tumors that express CEA. Int. J. Cancer 80:92–97, 1999. © 1999 Wiley‐Liss, Inc.
Carcinoembryonic antigen (CEA), which is expressed in several cancer types, is a potential target for specific immunotherapy. HLA-A24 is the most frequent allele among Japanese and is also frequently present in Asians and Caucasians. We tested CEA-encoded HLA-A24 binding peptides for their capacity to elicit anti-tumor cytotoxic T lymphocytes (CTL) in vitro. For this purpose, we used CD8 ؉ T lymphocytes from peripheral blood mononuclear cells (PBMC) of a healthy donor and autologous peptide-pulsed dendritic cells as antigenpresenting cells. This approach enabled us to identify 2 peptides, QYSWFVNGTF and TYACFVSNL, which were capable of eliciting CTL lines that lysed tumor cells expressing HLA-A24 and CEA. The cytotoxicity to tumor cells by the CTL lines was antigen-specific since it was inhibited by peptide-pulsed cold target cells as well as by anti-class I major histocompatibility complex (MHC) and anti-CD3 monoclonal antibodies (MAbs). The antigen specificity of the 2 CTL lines was examined using several tumor cell lines of various origins and for their peptide-dose responses. The identification of these novel CEA epitopes for CTL offers the opportunity to design and develop epitope-based immunotherapeutic approaches for treating HLA-A24 ؉ patients with tumors that express CEA. Int. J. Cancer 80:92-97, 1999.
Carcinoembryonic antigen (CEA), an oncofetal glycoprotein overexpressed in most gastrointestinal and lung cancers, is a candidate molecule for cancer immunotherapy. Recently, a CEA-derived 9-mer peptide, CEA652 (TYACFVSNL), has been identified as the epitope of cytotoxic T lymphocytes restricted with human leukocyte antigen (HLA)-A24, which is present in 60% of the Japanese population and in some Caucasians. The authors performed a clinical study of a vaccine using autologous dendritic cells (DCs) pulsed with CEA652 and adjuvant cytokines, natural human interferon alpha (nhuIFN-alpha), and natural human tumor necrosis factor alpha (nhuTNF-alpha), for the treatment of patients with CEA-expressing advanced metastatic malignancies. Ten HLA-A24 patients with advanced digestive tract or lung cancer were enrolled in the study to assess toxicity, tolerability and immune responses to the vaccine. DCs were generated from plastic adherent monocytes of granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood mononuclear cells (PBMCs) in the presence of granulocyte/macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4). Generated DCs showing an immature phenotype were loaded with CEA652 and injected into patients intradermally and subcutaneously with 50% of the dose administered by each route every 2 weeks for a total of ten vaccinations. The total dose of administered DCs ranged from 2.7x10(7)cells to 1.6x10(8)cells. Adjuvant cytokines, i.e., 1x10(6) U/body of nhuIFN-alpha and nhuTNF-alpha, were administered to patients twice a week during the vaccination period. No severe toxicity directly attributable to the treatment was observed, and the vaccine was well tolerated. In the delayed-type hypersensitivity (DTH) skin test, two patients showed a positive skin response to peptide-pulsed DCs after vaccination, although none of the patients tested positive prior to vaccination. In the two patients who showed a positive skin response disease remained stable for 6 and 9 months respectively. These results suggest that active immunization using DCs pulsed with CEA652 peptide in combination with the administration of adjuvant cytokines is a safe and feasible treatment procedure.
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