The Experts below are selected from a list of 66159 Experts worldwide ranked by ideXlab platform
Karlo Perica - One of the best experts on this subject based on the ideXlab platform.
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enrichment and expansion with nanoscale artificial Antigen Presenting Cells for adoptive immunotherapy
ACS Nano, 2015Co-Authors: Karlo Perica, Christian G Schutz, Mathias Oelke, Joan G Bieler, Juan Carlos Varela, Jacqueline Douglass, Andrew D Skora, Yenling Chiu, Kenneth W Kinzler, Shibin ZhouAbstract:Adoptive immunotherapy (AIT) can mediate durable regression of cancer, but widespread adoption of AIT is limited by the cost and complexity of generating tumor-specific T Cells. Here we develop an Enrichment + Expansion strategy using paramagnetic, nanoscale artificial Antigen Presenting Cells (aAPC) to rapidly expand tumor-specific T Cells from rare naive precursors and predicted neo-epitope responses. Nano-aAPC are capable of enriching rare tumor-specific T Cells in a magnetic column and subsequently activating them to induce proliferation. Enrichment + Expansion resulted in greater than 1000-fold expansion of both mouse and human tumor-specific T Cells in 1 week, with nano-aAPC based enrichment conferring a proliferation advantage during both in vitro culture and after adoptive transfer in vivo. Robust T cell responses were seen not only for shared tumor Antigens, but also for computationally predicted neo-epitopes. Streamlining the rapid generation of large numbers of tumor-specific T Cells in a cost-...
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biodegradable nanoellipsoidal artificial Antigen Presenting Cells for Antigen specific t cell activation
Small, 2015Co-Authors: Randall A Meyer, Joel C Sunshine, Karlo Perica, Alyssa K Kosmides, Jonathan P Schneck, Jordan J GreenAbstract:Biomimetic artificial Antigen Presenting Cells (aAPCs) have shown substantial promise as a platform for immune system activation and modulation. Antigen specific aAPCs reconstitute the critical T-Cell recognition (“signal 1”) and activation (“signal 2”) signals presented at the surface of APCs by Presenting peptide-in-MHC and positive costimulatory molecules such as anti-CD28 antibody on the surface of the particle. Classically, aAPCs are cell sized (2–10 µm), spherical particles, and have been made using a variety of materials, from liposomes[1, 2] to magnetic beads,[3–7] to non-degradable[8] and degradable polymeric microparticles.[9–11] Despite the extensive in vitro data supporting the efficacy of these particles in vitro, in vivo translation has been limited due to the poor bioavailability and activity of spherical micron sized particles. Nanoparticle systems offer an attractive alternative to micron sized particles as drug delivery vehicles for the aAPC platform. Recently, nanoparticles have been utilized for various therapeutic and diagnostic applications, such as tumor targeting and imaging.[12–16] Biodistribution of these drug carriers has been of special interest in the past few years, as efforts have been made to engineer nanoparticles that simultaneously target the region of interest and can be eliminated efficiently to avoid toxicity.[17–20]
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nanoscale artificial Antigen Presenting Cells for t cell immunotherapy
Nanomedicine: Nanotechnology Biology and Medicine, 2014Co-Authors: Karlo Perica, Joan G Bieler, Yenling Chiu, Andres De Leon Medero, Malarvizhi Durai, Leah V Sibener, Michaela Niemoller, Mario Assenmacher, Anne Richter, Michael EdidinAbstract:Abstract Artificial Antigen Presenting Cells (aAPC), which deliver stimulatory signals to cytotoxic lymphocytes, are a powerful tool for both adoptive and active immunotherapy. Thus far, aAPC have been synthesized by coupling T cell activating proteins such as CD3 or MHC-peptide to micron-sized beads. Nanoscale platforms have different trafficking and biophysical interaction properties and may allow development of new immunotherapeutic strategies. We therefore manufactured aAPC based on two types of nanoscale particle platforms: biocompatible iron-dextran paramagnetic particles (50-100nm in diameter) and avidin-coated quantum dot nanocrystals (~30nm). Nanoscale aAPC induced Antigen-specific T cell proliferation from mouse splenocytes and human peripheral blood T Cells. When injected in vivo, both iron-dextran particles and quantum dot nanocrystals enhanced tumor rejection in a subcutaneous mouse melanoma model. This is the first description of nanoscale aAPC that induce Antigen-specific T cell proliferation in vitro and lead to effective T cell stimulation and inhibition of tumor growth in vivo . From the Clinical Editor Artifical Antigen Presenting Cells could revolutionize the field of cancer-directed immunotherapy. This team of investigators have manufactured two types of nanoscale particle platform-based aAPCs and demonstrates that both iron-dextran particles and quantum dot nanocrystals enhance tumor rejection in a melanoma model, providing the first description of nanoscale aAPCs that lead to effective T cell stimulation and inhibition of tumor growth.
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particle shape dependence of cd8 t cell activation by artificial Antigen Presenting Cells
Biomaterials, 2014Co-Authors: Joel C Sunshine, Karlo Perica, Jonathan P Schneck, Jordan J GreenAbstract:Abstract Previous work developing particle-based acellular, artificial Antigen Presenting Cells (aAPCs) has focused exclusively on spherical platforms. To explore the role of shape, we generated ellipsoidal PLGA microparticles with varying aspect ratios (ARs) and synthesized aAPCs from them. The ellipsoidal biomimetic aAPCs with high-AR showed significantly enhanced in vitro and in vivo activity above spherical aAPCs with particle volume and Antigen content held constant. Confocal imaging indicates that CD8+ T Cells preferentially migrate to and are activated by interaction with the long axis of the aAPC. Importantly, enhanced activity of high-AR aAPCs was seen in a mouse melanoma model, with high-AR aAPCs improving melanoma survival compared to non-cognate aAPCs ( p = 0.004) and cognate spherical aAPCs ( p = 0.05). These findings indicate that particle geometry is a critical design criterion in the generation of aAPCs, and may offer insight into the essential role of geometry in the interaction between CD8+ T Cells and biological APCs.
Jordan J Green - One of the best experts on this subject based on the ideXlab platform.
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biodegradable nanoellipsoidal artificial Antigen Presenting Cells for Antigen specific t cell activation
Small, 2015Co-Authors: Randall A Meyer, Joel C Sunshine, Karlo Perica, Alyssa K Kosmides, Jonathan P Schneck, Jordan J GreenAbstract:Biomimetic artificial Antigen Presenting Cells (aAPCs) have shown substantial promise as a platform for immune system activation and modulation. Antigen specific aAPCs reconstitute the critical T-Cell recognition (“signal 1”) and activation (“signal 2”) signals presented at the surface of APCs by Presenting peptide-in-MHC and positive costimulatory molecules such as anti-CD28 antibody on the surface of the particle. Classically, aAPCs are cell sized (2–10 µm), spherical particles, and have been made using a variety of materials, from liposomes[1, 2] to magnetic beads,[3–7] to non-degradable[8] and degradable polymeric microparticles.[9–11] Despite the extensive in vitro data supporting the efficacy of these particles in vitro, in vivo translation has been limited due to the poor bioavailability and activity of spherical micron sized particles. Nanoparticle systems offer an attractive alternative to micron sized particles as drug delivery vehicles for the aAPC platform. Recently, nanoparticles have been utilized for various therapeutic and diagnostic applications, such as tumor targeting and imaging.[12–16] Biodistribution of these drug carriers has been of special interest in the past few years, as efforts have been made to engineer nanoparticles that simultaneously target the region of interest and can be eliminated efficiently to avoid toxicity.[17–20]
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particle shape dependence of cd8 t cell activation by artificial Antigen Presenting Cells
Biomaterials, 2014Co-Authors: Joel C Sunshine, Karlo Perica, Jonathan P Schneck, Jordan J GreenAbstract:Abstract Previous work developing particle-based acellular, artificial Antigen Presenting Cells (aAPCs) has focused exclusively on spherical platforms. To explore the role of shape, we generated ellipsoidal PLGA microparticles with varying aspect ratios (ARs) and synthesized aAPCs from them. The ellipsoidal biomimetic aAPCs with high-AR showed significantly enhanced in vitro and in vivo activity above spherical aAPCs with particle volume and Antigen content held constant. Confocal imaging indicates that CD8+ T Cells preferentially migrate to and are activated by interaction with the long axis of the aAPC. Importantly, enhanced activity of high-AR aAPCs was seen in a mouse melanoma model, with high-AR aAPCs improving melanoma survival compared to non-cognate aAPCs ( p = 0.004) and cognate spherical aAPCs ( p = 0.05). These findings indicate that particle geometry is a critical design criterion in the generation of aAPCs, and may offer insight into the essential role of geometry in the interaction between CD8+ T Cells and biological APCs.
Jean-paul Latgé - One of the best experts on this subject based on the ideXlab platform.
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correction corrigendum circulating human basophils lack the features of professional Antigen Presenting Cells
Scientific Reports, 2013Co-Authors: Meenu Sharma, Pushpa Hegde, Mohan S Maddur, Rémi Beau, Vishukumar Aimanianda, Hélène Sénéchal, Pascal Poncet, Jean-paul LatgéAbstract:Recent reports in mice demonstrate that basophils function as Antigen Presenting Cells (APC). They express MHC class II and co-stimulatory molecules CD80 and CD86, capture and present soluble Antigens or IgE-Antigen complexes and polarize Th2 responses. Therefore, we explored whether human circulating basophils possess the features of professional APC. We found that unlike dendritic Cells (DC) and monocytes, steady-state circulating human basophils did not express HLA-DR and co-stimulatory molecules CD80 and CD86. Basophils remained negative for these molecules following stimulation with soluble Asp f 1, one of the allergens of Aspergillus fumigatus; Bet v 1, the major birch allergen; TLR2-ligand or even upon IgE cross-linking. Unlike DC, Asp f 1-pulsed basophils did not promote Th2 responses as analyzed by the secretion of IL-4 in the basophil-CD4+ T cell co-culture. Together, these results demonstrate the inability of circulating human basophils to function as professional APC.
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circulating human basophils lack the features of professional Antigen Presenting Cells
Scientific Reports, 2013Co-Authors: Meenu Sharma, Pushpa Hegde, Mohan S Maddur, Rémi Beau, Vishukumar Aimanianda, Hélène Sénéchal, Pascal Poncet, Jean-paul LatgéAbstract:Recent reports in mice demonstrate that basophils function as Antigen Presenting Cells (APC). They express MHC class II and co-stimulatory molecules CD80 and CD86, capture and present soluble Antigens or IgE-Antigen complexes and polarize Th2 responses. Therefore, we explored whether human circulating basophils possess the features of professional APC. We found that unlike dendritic Cells (DC) and monocytes, steady-state circulating human basophils did not express HLA-DR and co-stimulatory molecules CD80 and CD86. Basophils remained negative for these molecules following stimulation with soluble Asp f 1, one of the allergens of Aspergillus fumigatus; Bet v 1, the major birch allergen; TLR2-ligand or even upon IgE cross-linking. Unlike DC, Asp f 1-pulsed basophils did not promote Th2 responses as analyzed by the secretion of IL-4 in the basophil-CD4+ T cell co-culture. Together, these results demonstrate the inability of circulating human basophils to function as professional APC.
Hélène Sénéchal - One of the best experts on this subject based on the ideXlab platform.
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correction corrigendum circulating human basophils lack the features of professional Antigen Presenting Cells
Scientific Reports, 2013Co-Authors: Meenu Sharma, Pushpa Hegde, Mohan S Maddur, Rémi Beau, Vishukumar Aimanianda, Hélène Sénéchal, Pascal Poncet, Jean-paul LatgéAbstract:Recent reports in mice demonstrate that basophils function as Antigen Presenting Cells (APC). They express MHC class II and co-stimulatory molecules CD80 and CD86, capture and present soluble Antigens or IgE-Antigen complexes and polarize Th2 responses. Therefore, we explored whether human circulating basophils possess the features of professional APC. We found that unlike dendritic Cells (DC) and monocytes, steady-state circulating human basophils did not express HLA-DR and co-stimulatory molecules CD80 and CD86. Basophils remained negative for these molecules following stimulation with soluble Asp f 1, one of the allergens of Aspergillus fumigatus; Bet v 1, the major birch allergen; TLR2-ligand or even upon IgE cross-linking. Unlike DC, Asp f 1-pulsed basophils did not promote Th2 responses as analyzed by the secretion of IL-4 in the basophil-CD4+ T cell co-culture. Together, these results demonstrate the inability of circulating human basophils to function as professional APC.
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circulating human basophils lack the features of professional Antigen Presenting Cells
Scientific Reports, 2013Co-Authors: Meenu Sharma, Pushpa Hegde, Mohan S Maddur, Rémi Beau, Vishukumar Aimanianda, Hélène Sénéchal, Pascal Poncet, Jean-paul LatgéAbstract:Recent reports in mice demonstrate that basophils function as Antigen Presenting Cells (APC). They express MHC class II and co-stimulatory molecules CD80 and CD86, capture and present soluble Antigens or IgE-Antigen complexes and polarize Th2 responses. Therefore, we explored whether human circulating basophils possess the features of professional APC. We found that unlike dendritic Cells (DC) and monocytes, steady-state circulating human basophils did not express HLA-DR and co-stimulatory molecules CD80 and CD86. Basophils remained negative for these molecules following stimulation with soluble Asp f 1, one of the allergens of Aspergillus fumigatus; Bet v 1, the major birch allergen; TLR2-ligand or even upon IgE cross-linking. Unlike DC, Asp f 1-pulsed basophils did not promote Th2 responses as analyzed by the secretion of IL-4 in the basophil-CD4+ T cell co-culture. Together, these results demonstrate the inability of circulating human basophils to function as professional APC.
Pascal Poncet - One of the best experts on this subject based on the ideXlab platform.
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correction corrigendum circulating human basophils lack the features of professional Antigen Presenting Cells
Scientific Reports, 2013Co-Authors: Meenu Sharma, Pushpa Hegde, Mohan S Maddur, Rémi Beau, Vishukumar Aimanianda, Hélène Sénéchal, Pascal Poncet, Jean-paul LatgéAbstract:Recent reports in mice demonstrate that basophils function as Antigen Presenting Cells (APC). They express MHC class II and co-stimulatory molecules CD80 and CD86, capture and present soluble Antigens or IgE-Antigen complexes and polarize Th2 responses. Therefore, we explored whether human circulating basophils possess the features of professional APC. We found that unlike dendritic Cells (DC) and monocytes, steady-state circulating human basophils did not express HLA-DR and co-stimulatory molecules CD80 and CD86. Basophils remained negative for these molecules following stimulation with soluble Asp f 1, one of the allergens of Aspergillus fumigatus; Bet v 1, the major birch allergen; TLR2-ligand or even upon IgE cross-linking. Unlike DC, Asp f 1-pulsed basophils did not promote Th2 responses as analyzed by the secretion of IL-4 in the basophil-CD4+ T cell co-culture. Together, these results demonstrate the inability of circulating human basophils to function as professional APC.
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circulating human basophils lack the features of professional Antigen Presenting Cells
Scientific Reports, 2013Co-Authors: Meenu Sharma, Pushpa Hegde, Mohan S Maddur, Rémi Beau, Vishukumar Aimanianda, Hélène Sénéchal, Pascal Poncet, Jean-paul LatgéAbstract:Recent reports in mice demonstrate that basophils function as Antigen Presenting Cells (APC). They express MHC class II and co-stimulatory molecules CD80 and CD86, capture and present soluble Antigens or IgE-Antigen complexes and polarize Th2 responses. Therefore, we explored whether human circulating basophils possess the features of professional APC. We found that unlike dendritic Cells (DC) and monocytes, steady-state circulating human basophils did not express HLA-DR and co-stimulatory molecules CD80 and CD86. Basophils remained negative for these molecules following stimulation with soluble Asp f 1, one of the allergens of Aspergillus fumigatus; Bet v 1, the major birch allergen; TLR2-ligand or even upon IgE cross-linking. Unlike DC, Asp f 1-pulsed basophils did not promote Th2 responses as analyzed by the secretion of IL-4 in the basophil-CD4+ T cell co-culture. Together, these results demonstrate the inability of circulating human basophils to function as professional APC.