The Experts below are selected from a list of 30 Experts worldwide ranked by ideXlab platform
Alfred E Chang - One of the best experts on this subject based on the ideXlab platform.
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immune response in human melanoma after transfer of an allogeneic class i major histocompatibility complex gene with dna liposome complexes
Proceedings of the National Academy of Sciences of the United States of America, 1996Co-Authors: Gary J Nabel, David Gordon, Keith D Bishop, Brian J Nickoloff, Zhiyong Yang, Atsushi Aruga, Mark J Cameron, Elizabeth G Nabel, Alfred E ChangAbstract:Analysis of the antitumor immune response after gene transfer of a foreign major histocompatibility complex class I Protein, HLA-B7, was performed. Ten HLA-B7-negative patients with stage IV melanoma were treated in an effort to stimulate local tumor immunity. Plasmid DNA was detected within treated tumor nodules, and RNA encoding recombinant HLA-B7 or HLA-B7 Protein was demonstrated in 9 of 10 patients. T cell migration into treated lesions was observed and tumor-infiltrating lymphocyte reactivity was enhanced in six of seven and two of two patients analyzed, respectively. In contrast, the frequency of cytotoxic T lymphocyte against autologous tumor in circulating peripheral blood lymphocytes was not altered significantly, suggesting that peripheral blood lymphocyte reactivity is not indicative of local tumor responsiveness. Local inhibition of tumor growth was detected after gene transfer in two patients, one of whom showed a partial remission. This patient subsequently received treatment with tumor-infiltrating lymphocytes derived from gene-modified tumor, with a complete regression of residual disease. Thus, gene transfer with DNA–liposome complexes encoding an allogeneic major histocompatibility complex Protein stimulated local antitumor immune responses that facilitated the generation of effector cells for immunotherapy of cancer.
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direct gene transfer with dna liposome complexes in melanoma expression biologic activity and lack of toxicity in humans
Proceedings of the National Academy of Sciences of the United States of America, 1993Co-Authors: Gary J Nabel, David Gordon, Zhiyong Yang, Elizabeth G Nabel, Bernard A Fox, Gregory E Plautz, Xiang Gao, Leaf Huang, Suyu Shu, Alfred E ChangAbstract:Abstract Direct gene transfer offers the potential to introduce DNA encoding therapeutic Proteins to treat human disease. Previously, gene transfer in humans has been achieved by a cell-mediated ex vivo approach in which cells from the blood or tissue of patients are genetically modified in the laboratory and subsequently returned to the patient. To determine the feasibility and safety of directly transferring genes into humans, a clinical study was performed. The gene encoding a foreign major histocompatibility complex Protein, HLA-B7, was introduced into HLA-B7-negative patients with advanced melanoma by injection of DNA-liposome complexes in an effort to demonstrate gene transfer, document recombinant gene expression, and determine the safety and potential toxicity of this therapy. Six courses of treatment were completed without complications in five HLA-B7-negative patients with stage IV melanoma. Plasmid DNA was detected within biopsies of treated tumor nodules 3-7 days after injection but was not found in the serum at any time by using the polymerase chain reaction. Recombinant HLA-B7 Protein was demonstrated in tumor biopsy tissue in all five patients by immunochemistry, and immune responses to HLA-B7 and autologous tumors could be detected. No antibodies to DNA were detected in any patient. One patient demonstrated regression of injected nodules on two independent treatments, which was accompanied by regression at distant sites. These studies demonstrate the feasibility, safety, and therapeutic potential of direct gene transfer in humans.
Xavier Estivill - One of the best experts on this subject based on the ideXlab platform.
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a common 56 kilobase deletion in a primate specific segmental duplication creates a novel butyrophilin like Protein
BMC Genetics, 2013Co-Authors: Johanna Aigner, Sergi Villatoro, Raquel Rabionet, Jaume Roquer, Jordi Jimenezconde, Eulalia Marti, Xavier EstivillAbstract:The Butyrophilin-like (BTNL) Proteins are likely to play an important role in inflammation and immune response. Like the B7 Protein family, many human and murine BTNL members have been shown to control T lymphocytes response, and polymorphisms in human BTNL2 have been linked to several inflammatory diseases, such as pulmonary sarcoidosis, inflammatory bowel disease and neonatal lupus. In this study we provide a comprehensive population, genomic and transcriptomic analysis of a 56-kb deletion copy number variant (CNV), located within two segmental duplications of two genes belonging to the BTNL family, namely BTNL8 and BTNL3. We confirm the presence of a novel BTNL8*3 fusion-Protein product, and show an influence of the deletion variant on the expression level of several genes involved in immune function, including BTNL9, another member of the same family. Moreover, by genotyping HapMap and human diversity panel (HGDP) samples, we demonstrate a clear difference in the stratification of the BTNL8_BTNL3-del allele frequency between major continental human populations. Despite tremendous progress in the field of structural variation, rather few CNVs have been functionally characterized so far. Here, we show clear functional consequences of a new deletion CNV (BTNL8_BTNL3-del) with potentially important implication in the human immune system and in inflammatory and proliferative disorders. In addition, the marked population differences found of BTNL8_BTNL3-del frequencies suggest that this deletion CNV might have evolved under positive selection due to environmental conditions in some populations, with potential phenotypic consequences.
Gary J Nabel - One of the best experts on this subject based on the ideXlab platform.
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immune response in human melanoma after transfer of an allogeneic class i major histocompatibility complex gene with dna liposome complexes
Proceedings of the National Academy of Sciences of the United States of America, 1996Co-Authors: Gary J Nabel, David Gordon, Keith D Bishop, Brian J Nickoloff, Zhiyong Yang, Atsushi Aruga, Mark J Cameron, Elizabeth G Nabel, Alfred E ChangAbstract:Analysis of the antitumor immune response after gene transfer of a foreign major histocompatibility complex class I Protein, HLA-B7, was performed. Ten HLA-B7-negative patients with stage IV melanoma were treated in an effort to stimulate local tumor immunity. Plasmid DNA was detected within treated tumor nodules, and RNA encoding recombinant HLA-B7 or HLA-B7 Protein was demonstrated in 9 of 10 patients. T cell migration into treated lesions was observed and tumor-infiltrating lymphocyte reactivity was enhanced in six of seven and two of two patients analyzed, respectively. In contrast, the frequency of cytotoxic T lymphocyte against autologous tumor in circulating peripheral blood lymphocytes was not altered significantly, suggesting that peripheral blood lymphocyte reactivity is not indicative of local tumor responsiveness. Local inhibition of tumor growth was detected after gene transfer in two patients, one of whom showed a partial remission. This patient subsequently received treatment with tumor-infiltrating lymphocytes derived from gene-modified tumor, with a complete regression of residual disease. Thus, gene transfer with DNA–liposome complexes encoding an allogeneic major histocompatibility complex Protein stimulated local antitumor immune responses that facilitated the generation of effector cells for immunotherapy of cancer.
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direct gene transfer with dna liposome complexes in melanoma expression biologic activity and lack of toxicity in humans
Proceedings of the National Academy of Sciences of the United States of America, 1993Co-Authors: Gary J Nabel, David Gordon, Zhiyong Yang, Elizabeth G Nabel, Bernard A Fox, Gregory E Plautz, Xiang Gao, Leaf Huang, Suyu Shu, Alfred E ChangAbstract:Abstract Direct gene transfer offers the potential to introduce DNA encoding therapeutic Proteins to treat human disease. Previously, gene transfer in humans has been achieved by a cell-mediated ex vivo approach in which cells from the blood or tissue of patients are genetically modified in the laboratory and subsequently returned to the patient. To determine the feasibility and safety of directly transferring genes into humans, a clinical study was performed. The gene encoding a foreign major histocompatibility complex Protein, HLA-B7, was introduced into HLA-B7-negative patients with advanced melanoma by injection of DNA-liposome complexes in an effort to demonstrate gene transfer, document recombinant gene expression, and determine the safety and potential toxicity of this therapy. Six courses of treatment were completed without complications in five HLA-B7-negative patients with stage IV melanoma. Plasmid DNA was detected within biopsies of treated tumor nodules 3-7 days after injection but was not found in the serum at any time by using the polymerase chain reaction. Recombinant HLA-B7 Protein was demonstrated in tumor biopsy tissue in all five patients by immunochemistry, and immune responses to HLA-B7 and autologous tumors could be detected. No antibodies to DNA were detected in any patient. One patient demonstrated regression of injected nodules on two independent treatments, which was accompanied by regression at distant sites. These studies demonstrate the feasibility, safety, and therapeutic potential of direct gene transfer in humans.
Johanna Aigner - One of the best experts on this subject based on the ideXlab platform.
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a common 56 kilobase deletion in a primate specific segmental duplication creates a novel butyrophilin like Protein
BMC Genetics, 2013Co-Authors: Johanna Aigner, Sergi Villatoro, Raquel Rabionet, Jaume Roquer, Jordi Jimenezconde, Eulalia Marti, Xavier EstivillAbstract:The Butyrophilin-like (BTNL) Proteins are likely to play an important role in inflammation and immune response. Like the B7 Protein family, many human and murine BTNL members have been shown to control T lymphocytes response, and polymorphisms in human BTNL2 have been linked to several inflammatory diseases, such as pulmonary sarcoidosis, inflammatory bowel disease and neonatal lupus. In this study we provide a comprehensive population, genomic and transcriptomic analysis of a 56-kb deletion copy number variant (CNV), located within two segmental duplications of two genes belonging to the BTNL family, namely BTNL8 and BTNL3. We confirm the presence of a novel BTNL8*3 fusion-Protein product, and show an influence of the deletion variant on the expression level of several genes involved in immune function, including BTNL9, another member of the same family. Moreover, by genotyping HapMap and human diversity panel (HGDP) samples, we demonstrate a clear difference in the stratification of the BTNL8_BTNL3-del allele frequency between major continental human populations. Despite tremendous progress in the field of structural variation, rather few CNVs have been functionally characterized so far. Here, we show clear functional consequences of a new deletion CNV (BTNL8_BTNL3-del) with potentially important implication in the human immune system and in inflammatory and proliferative disorders. In addition, the marked population differences found of BTNL8_BTNL3-del frequencies suggest that this deletion CNV might have evolved under positive selection due to environmental conditions in some populations, with potential phenotypic consequences.
Elizabeth G Nabel - One of the best experts on this subject based on the ideXlab platform.
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immune response in human melanoma after transfer of an allogeneic class i major histocompatibility complex gene with dna liposome complexes
Proceedings of the National Academy of Sciences of the United States of America, 1996Co-Authors: Gary J Nabel, David Gordon, Keith D Bishop, Brian J Nickoloff, Zhiyong Yang, Atsushi Aruga, Mark J Cameron, Elizabeth G Nabel, Alfred E ChangAbstract:Analysis of the antitumor immune response after gene transfer of a foreign major histocompatibility complex class I Protein, HLA-B7, was performed. Ten HLA-B7-negative patients with stage IV melanoma were treated in an effort to stimulate local tumor immunity. Plasmid DNA was detected within treated tumor nodules, and RNA encoding recombinant HLA-B7 or HLA-B7 Protein was demonstrated in 9 of 10 patients. T cell migration into treated lesions was observed and tumor-infiltrating lymphocyte reactivity was enhanced in six of seven and two of two patients analyzed, respectively. In contrast, the frequency of cytotoxic T lymphocyte against autologous tumor in circulating peripheral blood lymphocytes was not altered significantly, suggesting that peripheral blood lymphocyte reactivity is not indicative of local tumor responsiveness. Local inhibition of tumor growth was detected after gene transfer in two patients, one of whom showed a partial remission. This patient subsequently received treatment with tumor-infiltrating lymphocytes derived from gene-modified tumor, with a complete regression of residual disease. Thus, gene transfer with DNA–liposome complexes encoding an allogeneic major histocompatibility complex Protein stimulated local antitumor immune responses that facilitated the generation of effector cells for immunotherapy of cancer.
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direct gene transfer with dna liposome complexes in melanoma expression biologic activity and lack of toxicity in humans
Proceedings of the National Academy of Sciences of the United States of America, 1993Co-Authors: Gary J Nabel, David Gordon, Zhiyong Yang, Elizabeth G Nabel, Bernard A Fox, Gregory E Plautz, Xiang Gao, Leaf Huang, Suyu Shu, Alfred E ChangAbstract:Abstract Direct gene transfer offers the potential to introduce DNA encoding therapeutic Proteins to treat human disease. Previously, gene transfer in humans has been achieved by a cell-mediated ex vivo approach in which cells from the blood or tissue of patients are genetically modified in the laboratory and subsequently returned to the patient. To determine the feasibility and safety of directly transferring genes into humans, a clinical study was performed. The gene encoding a foreign major histocompatibility complex Protein, HLA-B7, was introduced into HLA-B7-negative patients with advanced melanoma by injection of DNA-liposome complexes in an effort to demonstrate gene transfer, document recombinant gene expression, and determine the safety and potential toxicity of this therapy. Six courses of treatment were completed without complications in five HLA-B7-negative patients with stage IV melanoma. Plasmid DNA was detected within biopsies of treated tumor nodules 3-7 days after injection but was not found in the serum at any time by using the polymerase chain reaction. Recombinant HLA-B7 Protein was demonstrated in tumor biopsy tissue in all five patients by immunochemistry, and immune responses to HLA-B7 and autologous tumors could be detected. No antibodies to DNA were detected in any patient. One patient demonstrated regression of injected nodules on two independent treatments, which was accompanied by regression at distant sites. These studies demonstrate the feasibility, safety, and therapeutic potential of direct gene transfer in humans.
