The Experts below are selected from a list of 69 Experts worldwide ranked by ideXlab platform
H. Trent Spencer - One of the best experts on this subject based on the ideXlab platform.
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Treatment of a Solid Tumor Using Engineered Drug-Resistant Immunocompetent Cells and Cytotoxic Chemotherapy
Human gene therapy, 2012Co-Authors: Anindya Dasgupta, Jordan E Shields, H. Trent SpencerAbstract:Multimodal therapy approaches, such as combining chemotherapy agents with Cellular immunotherapy, suffers from potential drug-mediated toxicity to immune effector Cells. Overcoming such toxic effects of anticancer Cellular products is a potential critical barrier to the development of combined therapeutic approaches. We are evaluating an anticancer strategy that focuses on overcoming such a barrier by genetically engineering drug-resistant variants of Immunocompetent Cells, thereby allowing for the coadministration of Cellular therapy with cytotoxic chemotherapy, a method we refer to as drug-resistant immunotherapy (DRI). The strategy relies on the use of cDNA sequences that confer drug resistance and recombinant lentiviral vectors to transfer nucleic acid sequences into Immunocompetent Cells. In the present study, we evaluated a DRI-based strategy that incorporates the Immunocompetent Cell line NK-92, which has intrinsic antitumor properties, genetically engineered to be resistant to both temozolomide and trimetrexate. These immune effector Cells efficiently lysed neuroblastoma Cell lines, which we show are also sensitive to both chemotherapy agents. The antitumor efficacy of the DRI strategy was demonstrated in vivo, whereby neuroblastoma-bearing NOD/SCID/γ-chain knockout (NSG) mice treated with dual drug-resistant NK-92 Cell therapy followed by dual cytotoxic chemotherapy showed tumor regression and significantly enhanced survival compared with animals receiving either nonengineered Cell-based therapy and chemotherapy, immunotherapy alone, or chemotherapy alone. These data show there is a benefit to using drug-resistant Cellular therapy when combined with cytotoxic chemotherapy approaches.
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Engineered drug-resistant Immunocompetent Cells enhance tumor Cell killing during a chemotherapy challenge.
Biochemical and biophysical research communications, 2009Co-Authors: Anindya Dasgupta, David Mccarty, H. Trent SpencerAbstract:Establishment of Immunocompetent Cell mediated anti-tumor immunity is often mitigated by the myelosuppressive effects during administration of chemotherapy. We hypothesized that protecting these immune Cells from drug induced toxicities may allow for the combined administration of immunotherapy and chemotherapy. Using a SIV-based lentiviral gene transfer system we delivered the drug-resistant variant P140KMGMT into the Immunocompetent Cell lines NK-92 and TALL-104, and the myelogenous leukemia Cell line, K562, which is a target for both NK-92 and TALL-104 Cells. Genetically engineered Immunocompetent Cells developed significant resistance to temozolomide compared to non-modified Cells, and genetic modification of these Cells did not affect their ability to kill K562 Cells. We then evaluated the effectiveness of drug-resistant Immunocompetent Cell mediated killing of tumor Cells in the presence and absence of chemotherapy. During a chemotherapy challenge the cytotoxic activity of non-modified Immunocompetent Cells was dramatically impaired. However, when combined with chemotherapy, genetically-modified immune Cells retained their cytotoxic activities and efficiently killed non-modified target Cells. These results show that engineering Immunocompetent Cells to withstand chemotherapy challenges can enhance tumor Cell killing when chemotherapy is applied in conjunction with Cell-based immunotherapy.
Anindya Dasgupta - One of the best experts on this subject based on the ideXlab platform.
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Treatment of a Solid Tumor Using Engineered Drug-Resistant Immunocompetent Cells and Cytotoxic Chemotherapy
Human gene therapy, 2012Co-Authors: Anindya Dasgupta, Jordan E Shields, H. Trent SpencerAbstract:Multimodal therapy approaches, such as combining chemotherapy agents with Cellular immunotherapy, suffers from potential drug-mediated toxicity to immune effector Cells. Overcoming such toxic effects of anticancer Cellular products is a potential critical barrier to the development of combined therapeutic approaches. We are evaluating an anticancer strategy that focuses on overcoming such a barrier by genetically engineering drug-resistant variants of Immunocompetent Cells, thereby allowing for the coadministration of Cellular therapy with cytotoxic chemotherapy, a method we refer to as drug-resistant immunotherapy (DRI). The strategy relies on the use of cDNA sequences that confer drug resistance and recombinant lentiviral vectors to transfer nucleic acid sequences into Immunocompetent Cells. In the present study, we evaluated a DRI-based strategy that incorporates the Immunocompetent Cell line NK-92, which has intrinsic antitumor properties, genetically engineered to be resistant to both temozolomide and trimetrexate. These immune effector Cells efficiently lysed neuroblastoma Cell lines, which we show are also sensitive to both chemotherapy agents. The antitumor efficacy of the DRI strategy was demonstrated in vivo, whereby neuroblastoma-bearing NOD/SCID/γ-chain knockout (NSG) mice treated with dual drug-resistant NK-92 Cell therapy followed by dual cytotoxic chemotherapy showed tumor regression and significantly enhanced survival compared with animals receiving either nonengineered Cell-based therapy and chemotherapy, immunotherapy alone, or chemotherapy alone. These data show there is a benefit to using drug-resistant Cellular therapy when combined with cytotoxic chemotherapy approaches.
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Engineered drug-resistant Immunocompetent Cells enhance tumor Cell killing during a chemotherapy challenge.
Biochemical and biophysical research communications, 2009Co-Authors: Anindya Dasgupta, David Mccarty, H. Trent SpencerAbstract:Establishment of Immunocompetent Cell mediated anti-tumor immunity is often mitigated by the myelosuppressive effects during administration of chemotherapy. We hypothesized that protecting these immune Cells from drug induced toxicities may allow for the combined administration of immunotherapy and chemotherapy. Using a SIV-based lentiviral gene transfer system we delivered the drug-resistant variant P140KMGMT into the Immunocompetent Cell lines NK-92 and TALL-104, and the myelogenous leukemia Cell line, K562, which is a target for both NK-92 and TALL-104 Cells. Genetically engineered Immunocompetent Cells developed significant resistance to temozolomide compared to non-modified Cells, and genetic modification of these Cells did not affect their ability to kill K562 Cells. We then evaluated the effectiveness of drug-resistant Immunocompetent Cell mediated killing of tumor Cells in the presence and absence of chemotherapy. During a chemotherapy challenge the cytotoxic activity of non-modified Immunocompetent Cells was dramatically impaired. However, when combined with chemotherapy, genetically-modified immune Cells retained their cytotoxic activities and efficiently killed non-modified target Cells. These results show that engineering Immunocompetent Cells to withstand chemotherapy challenges can enhance tumor Cell killing when chemotherapy is applied in conjunction with Cell-based immunotherapy.
Wayne K. Stadelmann - One of the best experts on this subject based on the ideXlab platform.
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Lymphadenectomy prior to rat hind limb allotransplantation prevents graft-versus-host disease in chimeric hosts
Transplant International, 2004Co-Authors: Pascal C. R. Brouha, Gustavo Perez-abadia, Cedric G. Francois, Luis A. Laurentin-perez, Vijay Gorantla, Marieke Vossen, Chau Tai, Diane Pidwell, Gary L. Anderson, Wayne K. StadelmannAbstract:In previous rat studies, the use of mixed allogeneic chimerism (MAC) to induce host tolerance to hind limb allografts has resulted in severe graft-versus-host disease (GVHD). The purpose of this study was to determine if Immunocompetent Cells in bone marrow (BM) and/or lymph nodes (LNs) of transplanted limbs were responsible for inducing GVHD in mixed chimeric hosts. [ACI→Wistar Furth] chimeric rats received ACI hind limbs that were non-irradiated, irradiated (1050 cGy) or lymphadenectomized. Rejection, GVHD and donor chimerism was assessed. Chimeric hosts rejected none of their limbs. However, hosts of non-irradiated hind limbs succumbed to GVHD 22.4±0.8 days after transplantation. In contrast, chimeras that received irradiated or lymphadenectomized ACI hind limbs showed no clinical or histological signs of GVHD at 5 months. We conclude that mixed chimeric hosts are susceptible to GVHD due to the Immunocompetent Cell load provided by the LNs, not the BM, of hind limb allografts.
Pascal C. R. Brouha - One of the best experts on this subject based on the ideXlab platform.
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Lymphadenectomy prior to rat hind limb allotransplantation prevents graft-versus-host disease in chimeric hosts
Transplant International, 2004Co-Authors: Pascal C. R. Brouha, Gustavo Perez-abadia, Cedric G. Francois, Luis A. Laurentin-perez, Vijay Gorantla, Marieke Vossen, Chau Tai, Diane Pidwell, Gary L. Anderson, Wayne K. StadelmannAbstract:In previous rat studies, the use of mixed allogeneic chimerism (MAC) to induce host tolerance to hind limb allografts has resulted in severe graft-versus-host disease (GVHD). The purpose of this study was to determine if Immunocompetent Cells in bone marrow (BM) and/or lymph nodes (LNs) of transplanted limbs were responsible for inducing GVHD in mixed chimeric hosts. [ACI→Wistar Furth] chimeric rats received ACI hind limbs that were non-irradiated, irradiated (1050 cGy) or lymphadenectomized. Rejection, GVHD and donor chimerism was assessed. Chimeric hosts rejected none of their limbs. However, hosts of non-irradiated hind limbs succumbed to GVHD 22.4±0.8 days after transplantation. In contrast, chimeras that received irradiated or lymphadenectomized ACI hind limbs showed no clinical or histological signs of GVHD at 5 months. We conclude that mixed chimeric hosts are susceptible to GVHD due to the Immunocompetent Cell load provided by the LNs, not the BM, of hind limb allografts.
Jordan E Shields - One of the best experts on this subject based on the ideXlab platform.
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Treatment of a Solid Tumor Using Engineered Drug-Resistant Immunocompetent Cells and Cytotoxic Chemotherapy
Human gene therapy, 2012Co-Authors: Anindya Dasgupta, Jordan E Shields, H. Trent SpencerAbstract:Multimodal therapy approaches, such as combining chemotherapy agents with Cellular immunotherapy, suffers from potential drug-mediated toxicity to immune effector Cells. Overcoming such toxic effects of anticancer Cellular products is a potential critical barrier to the development of combined therapeutic approaches. We are evaluating an anticancer strategy that focuses on overcoming such a barrier by genetically engineering drug-resistant variants of Immunocompetent Cells, thereby allowing for the coadministration of Cellular therapy with cytotoxic chemotherapy, a method we refer to as drug-resistant immunotherapy (DRI). The strategy relies on the use of cDNA sequences that confer drug resistance and recombinant lentiviral vectors to transfer nucleic acid sequences into Immunocompetent Cells. In the present study, we evaluated a DRI-based strategy that incorporates the Immunocompetent Cell line NK-92, which has intrinsic antitumor properties, genetically engineered to be resistant to both temozolomide and trimetrexate. These immune effector Cells efficiently lysed neuroblastoma Cell lines, which we show are also sensitive to both chemotherapy agents. The antitumor efficacy of the DRI strategy was demonstrated in vivo, whereby neuroblastoma-bearing NOD/SCID/γ-chain knockout (NSG) mice treated with dual drug-resistant NK-92 Cell therapy followed by dual cytotoxic chemotherapy showed tumor regression and significantly enhanced survival compared with animals receiving either nonengineered Cell-based therapy and chemotherapy, immunotherapy alone, or chemotherapy alone. These data show there is a benefit to using drug-resistant Cellular therapy when combined with cytotoxic chemotherapy approaches.