The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
James J. Moon - One of the best experts on this subject based on the ideXlab platform.
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Cancer nanomedicine for combination Cancer Immunotherapy
Nature Reviews Materials, 2019Co-Authors: Kyung Soo Park, Lonnie D. Shea, James J. MoonAbstract:Cancer Immunotherapy is revolutionizing oncology. However, dose-limiting toxicities and low patient response rates remain major challenges in the clinic. Cancer nanomedicine in combination with immunotherapies offers the possibility to amplify antitumour immune responses and to sensitize tumours to immunotherapies in a safe and effective manner. In this Review, we discuss opportunities for combination Immunotherapy based on nanoparticle platforms designed for chemotherapy, photothermal therapy, photodynamic therapy, radiotherapy and gene therapy. We highlight how nanoparticles can be used to reprogramme the immunosuppressive tumour microenvironment and to trigger systemic antitumour immunity, synergizing with immunotherapies against advanced Cancer. Finally, we discuss strategies to improve tumour and immune cell targeting while minimizing toxicity and immune-related adverse events, and we explore the potential of theranostic nanoparticles for combination Immunotherapy. Cancer nanomedicine in combination with immunotherapies offers the possibility to amplify antitumour immune responses and to sensitize tumours to immunotherapies. In this Review, the authors discuss combination Immunotherapy based on nanoparticle platforms designed for chemotherapy, photothermal therapy, photodynamic therapy, radiotherapy and gene therapy.
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subcutaneous nanodisc vaccination with neoantigens for combination Cancer Immunotherapy
Bioconjugate Chemistry, 2018Co-Authors: Rui Kuai, Anna Schwendeman, Xiaoqi Sun, Wenmin Yuan, James J. MoonAbstract:While Cancer Immunotherapy provides new exciting treatment options for patients, there is an urgent need for new strategies that can synergize with immune checkpoint blockers and boost the patient response rates. We have developed a personalized vaccine nanodisc platform based on synthetic high-density lipoproteins for co-delivery of immunostimulatory agents and tumor antigens, including tumor-specific neoantigens. Here we examined the route of delivery, safety profiles, and therapeutic efficacy of nanodisc vaccination against established tumors. We report that nanodiscs administered via the subcutaneous (SC) or intramuscular (IM) routes were well tolerated in mice without any signs of toxicity. The SC route significantly enhanced nanoparticle delivery to draining lymph nodes, improved nanodisc uptake by antigen-presenting cells, and generated 7-fold higher frequency of neoantigen-specific T cells, compared with the IM route. Importantly, when mice bearing advanced B16F10 melanoma tumors were treated with...
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designer vaccine nanodiscs for personalized Cancer Immunotherapy
Nature Materials, 2017Co-Authors: Rui Kuai, Anna Schwendeman, Lukasz J Ochyl, Keith S Bahjat, James J. MoonAbstract:Despite the tremendous potential of peptide-based Cancer vaccines, their efficacy has been limited in humans. Recent innovations in tumour exome sequencing have signalled the new era of personalized Immunotherapy with patient-specific neoantigens, but a general methodology for stimulating strong CD8α+ cytotoxic T-lymphocyte (CTL) responses remains lacking. Here we demonstrate that high-density lipoprotein-mimicking nanodiscs coupled with antigen (Ag) peptides and adjuvants can markedly improve Ag/adjuvant co-delivery to lymphoid organs and sustain Ag presentation on dendritic cells. Strikingly, nanodiscs elicited up to 47-fold greater frequencies of neoantigen-specific CTLs than soluble vaccines and even 31-fold greater than perhaps the strongest adjuvant in clinical trials (that is, CpG in Montanide). Moreover, multi-epitope vaccination generated broad-spectrum T-cell responses that potently inhibited tumour growth. Nanodiscs eliminated established MC-38 and B16F10 tumours when combined with anti-PD-1 and anti-CTLA-4 therapy. These findings represent a new powerful approach for Cancer Immunotherapy and suggest a general strategy for personalized nanomedicine.
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designer vaccine nanodiscs for personalized Cancer Immunotherapy
Nature Materials, 2017Co-Authors: Rui Kuai, Anna Schwendeman, Lukasz J Ochyl, Keith S Bahjat, James J. MoonAbstract:Despite the tremendous potential of peptide-based Cancer vaccines, their efficacy has been limited in humans. Recent innovations in tumour exome sequencing have signalled the new era of personalized Immunotherapy with patient-specific neoantigens, but a general methodology for stimulating strong CD8α+ cytotoxic T-lymphocyte (CTL) responses remains lacking. Here we demonstrate that high-density lipoprotein-mimicking nanodiscs coupled with antigen (Ag) peptides and adjuvants can markedly improve Ag/adjuvant co-delivery to lymphoid organs and sustain Ag presentation on dendritic cells. Strikingly, nanodiscs elicited up to 47-fold greater frequencies of neoantigen-specific CTLs than soluble vaccines and even 31-fold greater than perhaps the strongest adjuvant in clinical trials (that is, CpG in Montanide). Moreover, multi-epitope vaccination generated broad-spectrum T-cell responses that potently inhibited tumour growth. Nanodiscs eliminated established MC-38 and B16F10 tumours when combined with anti-PD-1 and anti-CTLA-4 therapy. These findings represent a new powerful approach for Cancer Immunotherapy and suggest a general strategy for personalized nanomedicine. High-density lipoprotein nanodiscs loaded with immunostimulatory biomolecules can target draining lymph nodes for Cancer vaccination.
Al-ola Abdallah - One of the best experts on this subject based on the ideXlab platform.
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a novel prostate Cancer Immunotherapy using prostate specific antigen peptides and candida skin test reagent as an adjuvant
Sage Open Medicine, 2018Co-Authors: Al-ola Abdallah, Mohamed Kamel, Rodney Davis, Teri Landrum, Hannah N Coleman, Horace J Spencer, Samuel G Mackintosh, Fade MahmoudAbstract:Objectives Our group developed the use of the Candida skin test reagent as an adjuvant of cell-mediated immunity in designing a human papillomavirus therapeutic vaccine. Here, this technology is being applied for designing a prostate Cancer Immunotherapy. Methods Peptides based on the prostate-specific antigen amino acid sequences were selected, synthesized, and evaluated in terms of their (1) solubility, (2) maturation effects on Langerhans cells by fluorescence-activated cell sorter analysis, and (3) recognition by peripheral immune cells from prostate Cancer patients using interferon-γ enzyme-linked immunospot assay. Results The peptides were soluble in 10 mM succinate at pH of 5 with 5% glycine, and they demonstrated no maturation effects on Langerhans cells from healthy donors. On the other hand, peripheral immune cells from 4 of 10 prostate Cancer patients examined had positive responses in enzyme-linked immunospot assay to one or more prostate-specific antigen peptides. Conclusion In summary, a design and a formulation of a novel prostate Cancer Immunotherapy are described. The immunogenicity of prostate-specific antigen peptides in some prostate Cancer patients supports further development of this Immunotherapy.
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A novel prostate Cancer Immunotherapy using prostate-specific antigen peptides and skin test reagent as an adjuvant
SAGE Publishing, 2018Co-Authors: Al-ola Abdallah, Hannah Coleman, Mohamed Kamel, Rodney Davis, Teri Landrum, Horace Spencer, Sam Mackintosh, Fade A Mahmoud, Natasa Milojkovic, Chester WickerAbstract:Objectives: Our group developed the use of the Candida skin test reagent as an adjuvant of cell-mediated immunity in designing a human papillomavirus therapeutic vaccine. Here, this technology is being applied for designing a prostate Cancer Immunotherapy. Methods: Peptides based on the prostate-specific antigen amino acid sequences were selected, synthesized, and evaluated in terms of their (1) solubility, (2) maturation effects on Langerhans cells by fluorescence-activated cell sorter analysis, and (3) recognition by peripheral immune cells from prostate Cancer patients using interferon-γ enzyme-linked immunospot assay. Results: The peptides were soluble in 10 mM succinate at pH of 5 with 5% glycine, and they demonstrated no maturation effects on Langerhans cells from healthy donors. On the other hand, peripheral immune cells from 4 of 10 prostate Cancer patients examined had positive responses in enzyme-linked immunospot assay to one or more prostate-specific antigen peptides. Conclusion: In summary, a design and a formulation of a novel prostate Cancer Immunotherapy are described. The immunogenicity of prostate-specific antigen peptides in some prostate Cancer patients supports further development of this Immunotherapy
Mohamed Kamel - One of the best experts on this subject based on the ideXlab platform.
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a novel prostate Cancer Immunotherapy using prostate specific antigen peptides and candida skin test reagent as an adjuvant
Sage Open Medicine, 2018Co-Authors: Al-ola Abdallah, Mohamed Kamel, Rodney Davis, Teri Landrum, Hannah N Coleman, Horace J Spencer, Samuel G Mackintosh, Fade MahmoudAbstract:Objectives Our group developed the use of the Candida skin test reagent as an adjuvant of cell-mediated immunity in designing a human papillomavirus therapeutic vaccine. Here, this technology is being applied for designing a prostate Cancer Immunotherapy. Methods Peptides based on the prostate-specific antigen amino acid sequences were selected, synthesized, and evaluated in terms of their (1) solubility, (2) maturation effects on Langerhans cells by fluorescence-activated cell sorter analysis, and (3) recognition by peripheral immune cells from prostate Cancer patients using interferon-γ enzyme-linked immunospot assay. Results The peptides were soluble in 10 mM succinate at pH of 5 with 5% glycine, and they demonstrated no maturation effects on Langerhans cells from healthy donors. On the other hand, peripheral immune cells from 4 of 10 prostate Cancer patients examined had positive responses in enzyme-linked immunospot assay to one or more prostate-specific antigen peptides. Conclusion In summary, a design and a formulation of a novel prostate Cancer Immunotherapy are described. The immunogenicity of prostate-specific antigen peptides in some prostate Cancer patients supports further development of this Immunotherapy.
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A novel prostate Cancer Immunotherapy using prostate-specific antigen peptides and skin test reagent as an adjuvant
SAGE Publishing, 2018Co-Authors: Al-ola Abdallah, Hannah Coleman, Mohamed Kamel, Rodney Davis, Teri Landrum, Horace Spencer, Sam Mackintosh, Fade A Mahmoud, Natasa Milojkovic, Chester WickerAbstract:Objectives: Our group developed the use of the Candida skin test reagent as an adjuvant of cell-mediated immunity in designing a human papillomavirus therapeutic vaccine. Here, this technology is being applied for designing a prostate Cancer Immunotherapy. Methods: Peptides based on the prostate-specific antigen amino acid sequences were selected, synthesized, and evaluated in terms of their (1) solubility, (2) maturation effects on Langerhans cells by fluorescence-activated cell sorter analysis, and (3) recognition by peripheral immune cells from prostate Cancer patients using interferon-γ enzyme-linked immunospot assay. Results: The peptides were soluble in 10 mM succinate at pH of 5 with 5% glycine, and they demonstrated no maturation effects on Langerhans cells from healthy donors. On the other hand, peripheral immune cells from 4 of 10 prostate Cancer patients examined had positive responses in enzyme-linked immunospot assay to one or more prostate-specific antigen peptides. Conclusion: In summary, a design and a formulation of a novel prostate Cancer Immunotherapy are described. The immunogenicity of prostate-specific antigen peptides in some prostate Cancer patients supports further development of this Immunotherapy
Rui Kuai - One of the best experts on this subject based on the ideXlab platform.
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subcutaneous nanodisc vaccination with neoantigens for combination Cancer Immunotherapy
Bioconjugate Chemistry, 2018Co-Authors: Rui Kuai, Anna Schwendeman, Xiaoqi Sun, Wenmin Yuan, James J. MoonAbstract:While Cancer Immunotherapy provides new exciting treatment options for patients, there is an urgent need for new strategies that can synergize with immune checkpoint blockers and boost the patient response rates. We have developed a personalized vaccine nanodisc platform based on synthetic high-density lipoproteins for co-delivery of immunostimulatory agents and tumor antigens, including tumor-specific neoantigens. Here we examined the route of delivery, safety profiles, and therapeutic efficacy of nanodisc vaccination against established tumors. We report that nanodiscs administered via the subcutaneous (SC) or intramuscular (IM) routes were well tolerated in mice without any signs of toxicity. The SC route significantly enhanced nanoparticle delivery to draining lymph nodes, improved nanodisc uptake by antigen-presenting cells, and generated 7-fold higher frequency of neoantigen-specific T cells, compared with the IM route. Importantly, when mice bearing advanced B16F10 melanoma tumors were treated with...
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designer vaccine nanodiscs for personalized Cancer Immunotherapy
Nature Materials, 2017Co-Authors: Rui Kuai, Anna Schwendeman, Lukasz J Ochyl, Keith S Bahjat, James J. MoonAbstract:Despite the tremendous potential of peptide-based Cancer vaccines, their efficacy has been limited in humans. Recent innovations in tumour exome sequencing have signalled the new era of personalized Immunotherapy with patient-specific neoantigens, but a general methodology for stimulating strong CD8α+ cytotoxic T-lymphocyte (CTL) responses remains lacking. Here we demonstrate that high-density lipoprotein-mimicking nanodiscs coupled with antigen (Ag) peptides and adjuvants can markedly improve Ag/adjuvant co-delivery to lymphoid organs and sustain Ag presentation on dendritic cells. Strikingly, nanodiscs elicited up to 47-fold greater frequencies of neoantigen-specific CTLs than soluble vaccines and even 31-fold greater than perhaps the strongest adjuvant in clinical trials (that is, CpG in Montanide). Moreover, multi-epitope vaccination generated broad-spectrum T-cell responses that potently inhibited tumour growth. Nanodiscs eliminated established MC-38 and B16F10 tumours when combined with anti-PD-1 and anti-CTLA-4 therapy. These findings represent a new powerful approach for Cancer Immunotherapy and suggest a general strategy for personalized nanomedicine.
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designer vaccine nanodiscs for personalized Cancer Immunotherapy
Nature Materials, 2017Co-Authors: Rui Kuai, Anna Schwendeman, Lukasz J Ochyl, Keith S Bahjat, James J. MoonAbstract:Despite the tremendous potential of peptide-based Cancer vaccines, their efficacy has been limited in humans. Recent innovations in tumour exome sequencing have signalled the new era of personalized Immunotherapy with patient-specific neoantigens, but a general methodology for stimulating strong CD8α+ cytotoxic T-lymphocyte (CTL) responses remains lacking. Here we demonstrate that high-density lipoprotein-mimicking nanodiscs coupled with antigen (Ag) peptides and adjuvants can markedly improve Ag/adjuvant co-delivery to lymphoid organs and sustain Ag presentation on dendritic cells. Strikingly, nanodiscs elicited up to 47-fold greater frequencies of neoantigen-specific CTLs than soluble vaccines and even 31-fold greater than perhaps the strongest adjuvant in clinical trials (that is, CpG in Montanide). Moreover, multi-epitope vaccination generated broad-spectrum T-cell responses that potently inhibited tumour growth. Nanodiscs eliminated established MC-38 and B16F10 tumours when combined with anti-PD-1 and anti-CTLA-4 therapy. These findings represent a new powerful approach for Cancer Immunotherapy and suggest a general strategy for personalized nanomedicine. High-density lipoprotein nanodiscs loaded with immunostimulatory biomolecules can target draining lymph nodes for Cancer vaccination.
Fade Mahmoud - One of the best experts on this subject based on the ideXlab platform.
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a novel prostate Cancer Immunotherapy using prostate specific antigen peptides and candida skin test reagent as an adjuvant
Sage Open Medicine, 2018Co-Authors: Al-ola Abdallah, Mohamed Kamel, Rodney Davis, Teri Landrum, Hannah N Coleman, Horace J Spencer, Samuel G Mackintosh, Fade MahmoudAbstract:Objectives Our group developed the use of the Candida skin test reagent as an adjuvant of cell-mediated immunity in designing a human papillomavirus therapeutic vaccine. Here, this technology is being applied for designing a prostate Cancer Immunotherapy. Methods Peptides based on the prostate-specific antigen amino acid sequences were selected, synthesized, and evaluated in terms of their (1) solubility, (2) maturation effects on Langerhans cells by fluorescence-activated cell sorter analysis, and (3) recognition by peripheral immune cells from prostate Cancer patients using interferon-γ enzyme-linked immunospot assay. Results The peptides were soluble in 10 mM succinate at pH of 5 with 5% glycine, and they demonstrated no maturation effects on Langerhans cells from healthy donors. On the other hand, peripheral immune cells from 4 of 10 prostate Cancer patients examined had positive responses in enzyme-linked immunospot assay to one or more prostate-specific antigen peptides. Conclusion In summary, a design and a formulation of a novel prostate Cancer Immunotherapy are described. The immunogenicity of prostate-specific antigen peptides in some prostate Cancer patients supports further development of this Immunotherapy.
