The Experts below are selected from a list of 7569 Experts worldwide ranked by ideXlab platform
Eli Gilboa - One of the best experts on this subject based on the ideXlab platform.
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the makings of a tumor rejection antigen
Immunity, 1999Co-Authors: Eli GilboaAbstract:If isolation of unique group I–type antigens from each cancer patients is not practical, and the use of shared nonmutated antigens must await the development of appropriate antigen isolation methodologies, what can one do in the meantime? One attrActive option is to vaccinate with autologous tumor-derived antigenic mixtures. The tumor-derived antigenic mixtures will include the complete antigenic repertoire of the tumor, including the potent group I patient-specific antigens, yet will obviate the need to identify the relevant tumor antigens in each patient. In animal tumor models, vaccination with genetically modified irradiated tumor cells (Gilboa and Lyerly 1994xSpecific Active Immunotherapy of cancer using genetically modified tumor vaccines. Gilboa, E and Lyerly, H.K. See all ReferencesGilboa and Lyerly 1994), tumor-derived heat shock proteins (Tamura et al. 1997xImmunotherapy of tumors with autologous tumor-derived heat shock protein preparations. Tamura, Y, Peng, P, Liu, K, Daou, M, and Srivastava, P.K. Science. 1997; 278: 117–120Crossref | PubMed | Scopus (578)See all ReferencesTamura et al. 1997), or with dendritic cells loaded with tumor-derived peptides or proteins (Gilboa et al. 1998xImmunotherapy of cancer with dendritic-cell based vaccines. Gilboa, E, Nair, S.K, and Lyerly, H.K. Cancer Immunol. Immunother. 1998; 46: 82–87Crossref | PubMed | Scopus (247)See all ReferencesGilboa et al. 1998) is very potent. A common limitation of these strategies is that sufficient tumor tissue for antigen preparation cannot be obtained or generated from many cancer patients. In such instances, use of mRNA amplified from small amounts of available tumor tissue could provide unlimited amounts of antigen for vacccination protocols.*E-mail: e.gilboa@cgct.duke.edu.
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induction of carcinoembryonic antigen cea specific cytotoxic t lymphocyte responses in vitro using autologous dendritic cells loaded with cea peptide or cea rna in patients with metastatic malignancies expressing cea
International Journal of Cancer, 1999Co-Authors: Smita K Nair, Eli Gilboa, Doris Coleman, S Hull, Kim H Lyerly, Michael A MorseAbstract:The application of dendritic cells (DC) to the Active Immunotherapy of cancer currently relies on the generation of potent DC capable of presenting tumor antigens such as carcinoembryonic antigen (CEA). It is unknown whether the T cells of patients with advanced malignancies can be reliably stimulated against tumor antigens by their autologous DC. In this study, starting with the peripheral blood mononuclear cells (PBMC) of patients with metastatic malignancies expressing CEA, autologous DCs were generated in vitro in serum-free media supplemented with GM-CSF and IL-4. The DCs from HLA A2 positive patients were loaded with the CEA peptide CAP-1 and the DCs from HLA A2 negative patients were depleted of bystander lymphocytes and loaded with mRNA encoding CEA. The DC preparations were tested to determine their phenotype and were used to stimulate autologous PBMC twice, separated by 10–14 days. The stimulated cells were then tested for their ability to lyse CEA-expressing target cells. We successfully generated an adequate number of DC for a clinical trial from all patients. The harvested DC preparations contained 49% DC and 87% DC if depleted of bystander lymphocytes. Phenotypic analysis showed the typical pattern of CD11c+CD40+CD86+HLA-DR+ CD80lowCD83lowCD14low. All preparations but one were able to stimulate CEA-specific cytotoxic T-lymphocyte (CTL) activity, suggesting that the majority of patients are not anergic to CEA and possess functional DC. The CTL activity was similar for the CEA peptide and CEA RNA-loaded DC. Int. J. Cancer 82:121–124, 1999. © 1999 Wiley-Liss, Inc.
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bone marrow generated dendritic cells pulsed with tumor extracts or tumor rna induce antitumor immunity against central nervous system tumors
Journal of Experimental Medicine, 1997Co-Authors: David M Ashley, Brenda Faiola, Smita K Nair, Laura P Hale, Darell D Bigner, Eli GilboaAbstract:Recent studies have shown that the brain is not a barrier to successful Active Immunotherapy that uses gene-modified autologous tumor cell vaccines. In this study, we compared the efficacy of two types of vaccines for the treatment of tumors within the central nervous system (CNS): dendritic cell (DC)-based vaccines pulsed with either tumor extract or tumor RNA, and cytokine gene–modified tumor vaccines. Using the B16/F10 murine melanoma (B16) as a model for CNS tumor, we show that vaccination with bone marrow–generated DCs, pulsed with either B16 cell extract or B16 total RNA, can induce specific cytotoxic T lymphocytes against B16 tumor cells. Both types of DC vaccines were able to protect animals from tumors located in the CNS. DC-based vaccines also led to prolonged survival in mice with tumors placed before the initiation of vaccine therapy. The DC-based vaccines were at least as effective, if not more so, as vaccines containing B16 tumor cells in which the granulocytic macrophage colony-stimulating factor gene had been modified. These data support the use of DC-based vaccines for the treatment of patients with CNS tumors.
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Immunotherapy of prostate cancer in the dunning rat model use of cytokine gene modified tumor vaccines
Cancer Research, 1994Co-Authors: Johannes Vieweg, Felicia M Rosenthal, Rajat Bannerji, Warren D W Heston, William R Fair, Bernd Gansbacher, Eli GilboaAbstract:Abstract Adenocarcinoma of the prostate is the most common cancer in men. The majority of cancers are discovered once they have already metastasized, and there is no effective therapy for prostatic cancer at this stage. The use of cytokine-secreting tumor cell preparations as therapeutic vaccines for the treatment of advanced prostate cancer was investigated in the Dunning rat R3327-MatLyLu prostatic tumor model. IL-2 secreting, irradiated, tumor cell preparations were capable of curing animals with s.c. established tumors, and induced immunological memory that protected animals from subsequent tumor challenge. Immunotherapy was less effective when tumors were induced orthotopically, but nevertheless led to improved outcome, significantly delaying, and occasionally preventing, recurrence of tumors after resection of the cancerous prostate. Granulocyte-macrophage colony stimulating factor secreting tumor cell preparations were less effective, and interferon-γ secreting cells had only a marginal effect. Induction of a potent immune response in tumor bearing animals against the nonimmunogenic MatLyLu tumor supports the view that Active Immunotherapy warrants further investigation as a potential therapeutic approach to prostate cancer.
Joel Plumas - One of the best experts on this subject based on the ideXlab platform.
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engineering a human plasmacytoid dendritic cell based vaccine to prime and expand multispecific viral and tumor antigen specific t cells
Vaccine, 2021Co-Authors: Kevin Lenogue, Alexandre Walencik, Karine Laulagnier, Jeanpaul Molens, Houssem Benlalam, Brigitte Dreno, Pierre Coulie, Martin Pule, Laurence Chaperot, Joel PlumasAbstract:Because dendritic cells are crucial to prime and expand antigen-specific CD8+ T-cells, several strategies are designed to use them in therapeutic vaccines against infectious diseases or cancer. In this context, off-the-shelf allogeneic dendritic cell-based platforms are more attrActive than individualized autologous vaccines tailored to each patient. In the present study, a unique dendritic cell line (PDC*line) platform of plasmacytoid origin, already used to prime and expand antitumor immunity in melanoma patients, was improved thanks to retroviral engineering. We demonstrated that the clinical-grade PDC*line, transduced with genes encoding viral or tumoral whole proteins, efficiently processed and stably presented the transduced antigens in different human leukocyte antigen (HLA) class I contexts. Moreover, the use of polyepitope constructs allowed the presentation of immunogenic peptides and the expansion of specific cytotoxic effectors. We also demonstrated that the addition of the Lysosome-associated membrane protein-1 (LAMP-1) sequence greatly improved the presentation of some peptides. Lastly, thanks to transduction of new HLA molecules, the PDC platform can benefit many patients through the easy addition of matched HLA-I molecules. The demonstration of the effective retroviral transduction of PDC*line cells strengthens and broadens the scope of the PDC*line platform, which can be used in adoptive or Active Immunotherapy for the treatment of infectious diseases or cancer.
Keith L Black - One of the best experts on this subject based on the ideXlab platform.
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antigen specific t cell response from dendritic cell vaccination using cancer stem like cell associated antigens
Stem Cells, 2009Co-Authors: Gentao Liu, Xiangpeng Yuan, Hongqiang Wang, Bindu Konda, Keith L BlackAbstract:Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor, with current treatment remaining palliative. Immunotherapies harness the body's own immune system to target cancers and could overcome the limitations of conventional treatments. One Active Immunotherapy strategy uses dendritic cell (DC)-based vaccination to initiate T-cell-mediated antitumor immunity. It has been proposed that cancer stem-like cells (CSCs) may play a key role in cancer initiation, progression, and resistance to current treatments. However, whether using human CSC antigens may improve the antitumor effect of DC vaccination against human cancer is unclear. In this study, we explored the suitability of CSCs as sources of antigens for DC vaccination again human GBM, with the aim of achieving CSC-targeting and enhanced antitumor immunity. We found that CSCs express high levels of tumor-associated antigens as well as major histocompatibility complex molecules. Furthermore, DC vaccination using CSC antigens elicited antigen-specific T-cell responses against CSCs. DC vaccination-induced interferon-gamma production is positively correlated with the number of antigen-specific T cells generated. Finally, using a 9L CSC brain tumor model, we demonstrate that vaccination with DCs loaded with 9L CSCs, but not daughter cells or conventionally cultured 9L cells, induced cytotoxic T lymphocytes (CTLs) against CSCs, and prolonged survival in animals bearing 9L CSC tumors. Understanding how immunization with CSCs generates superior antitumor immunity may accelerate development of CSC-specific immunotherapies and cancer vaccines.
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vaccination with tumor lysate pulsed dendritic cells elicits antigen specific cytotoxic t cells in patients with malignant glioma
Cancer Research, 2004Co-Authors: Gentao Liu, Keith L Black, Han Ying, William H Yong, Christopher J WheelerAbstract:The primary goal of this Phase I study was to assess the safety and bioactivity of tumor lysate-pulsed dendritic cell (DC) vaccination to treat patients with glioblastoma multiforme and anaplastic astrocytoma. Adverse events, survival, and cytotoxicity against autologous tumor and tumor-associated antigens were measured. Fourteen patients were thrice vaccinated 2 weeks apart with autologous DCs pulsed with tumor lysate. Peripheral blood mononuclear cells were differentiated into phenotypically and functionally confirmed DCs. Vaccination with tumor lysate-pulsed DCs was safe, and no evidence of autoimmune disease was noted. Ten patients were tested for the development of cytotoxicity through a quantitative PCR-based assay. Six of 10 patients demonstrated robust systemic cytotoxicity as demonstrated by IFN-gamma expression by peripheral blood mononuclear cells in response to tumor lysate after vaccination. Using HLA-restricted tetramer staining, we identified a significant expansion in CD8+ antigen-specific T-cell clones against one or more of tumor-associated antigens MAGE-1, gp100, and HER-2 after DC vaccination in four of nine patients. A significant CD8+ T-cell infiltrate was noted intratumorally in three of six patients who underwent reoperation. The median survival for patients with recurrent glioblastoma multiforme in this study (n = 8) was 133 weeks. This Phase I study demonstrated the feasibility, safety, and bioactivity of an autologous tumor lysate-pulsed DC vaccine for patients with malignant glioma. We demonstrate for the first time the ability of an Active Immunotherapy strategy to generate antigen-specific cytotoxicity in brain tumor patients.
Richard T Kenney - One of the best experts on this subject based on the ideXlab platform.
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immune response safety and survival impact from cmb305 in ny eso 1 recurrent soft tissue sarcomas sts
Journal of Clinical Oncology, 2017Co-Authors: Neeta Somaiah, Sant P Chawla, Matthew S Block, John C Morris, Joseph Kim, Mihaela Druta, Kamalesh Kumar Sankhala, Patrick Hwu, Sacha Gnjatic, Richard T KenneyAbstract:11006Background: CMB305 is an Active Immunotherapy regimen designed to generate and expand anti-NY-ESO-1 T cells. It consists of LV305, a dendritic cell targeting lentiviral vector encoding NY-ESO-...
Gentao Liu - One of the best experts on this subject based on the ideXlab platform.
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antigen specific t cell response from dendritic cell vaccination using cancer stem like cell associated antigens
Stem Cells, 2009Co-Authors: Gentao Liu, Xiangpeng Yuan, Hongqiang Wang, Bindu Konda, Keith L BlackAbstract:Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor, with current treatment remaining palliative. Immunotherapies harness the body's own immune system to target cancers and could overcome the limitations of conventional treatments. One Active Immunotherapy strategy uses dendritic cell (DC)-based vaccination to initiate T-cell-mediated antitumor immunity. It has been proposed that cancer stem-like cells (CSCs) may play a key role in cancer initiation, progression, and resistance to current treatments. However, whether using human CSC antigens may improve the antitumor effect of DC vaccination against human cancer is unclear. In this study, we explored the suitability of CSCs as sources of antigens for DC vaccination again human GBM, with the aim of achieving CSC-targeting and enhanced antitumor immunity. We found that CSCs express high levels of tumor-associated antigens as well as major histocompatibility complex molecules. Furthermore, DC vaccination using CSC antigens elicited antigen-specific T-cell responses against CSCs. DC vaccination-induced interferon-gamma production is positively correlated with the number of antigen-specific T cells generated. Finally, using a 9L CSC brain tumor model, we demonstrate that vaccination with DCs loaded with 9L CSCs, but not daughter cells or conventionally cultured 9L cells, induced cytotoxic T lymphocytes (CTLs) against CSCs, and prolonged survival in animals bearing 9L CSC tumors. Understanding how immunization with CSCs generates superior antitumor immunity may accelerate development of CSC-specific immunotherapies and cancer vaccines.
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vaccination with tumor lysate pulsed dendritic cells elicits antigen specific cytotoxic t cells in patients with malignant glioma
Cancer Research, 2004Co-Authors: Gentao Liu, Keith L Black, Han Ying, William H Yong, Christopher J WheelerAbstract:The primary goal of this Phase I study was to assess the safety and bioactivity of tumor lysate-pulsed dendritic cell (DC) vaccination to treat patients with glioblastoma multiforme and anaplastic astrocytoma. Adverse events, survival, and cytotoxicity against autologous tumor and tumor-associated antigens were measured. Fourteen patients were thrice vaccinated 2 weeks apart with autologous DCs pulsed with tumor lysate. Peripheral blood mononuclear cells were differentiated into phenotypically and functionally confirmed DCs. Vaccination with tumor lysate-pulsed DCs was safe, and no evidence of autoimmune disease was noted. Ten patients were tested for the development of cytotoxicity through a quantitative PCR-based assay. Six of 10 patients demonstrated robust systemic cytotoxicity as demonstrated by IFN-gamma expression by peripheral blood mononuclear cells in response to tumor lysate after vaccination. Using HLA-restricted tetramer staining, we identified a significant expansion in CD8+ antigen-specific T-cell clones against one or more of tumor-associated antigens MAGE-1, gp100, and HER-2 after DC vaccination in four of nine patients. A significant CD8+ T-cell infiltrate was noted intratumorally in three of six patients who underwent reoperation. The median survival for patients with recurrent glioblastoma multiforme in this study (n = 8) was 133 weeks. This Phase I study demonstrated the feasibility, safety, and bioactivity of an autologous tumor lysate-pulsed DC vaccine for patients with malignant glioma. We demonstrate for the first time the ability of an Active Immunotherapy strategy to generate antigen-specific cytotoxicity in brain tumor patients.
