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4 results on '"P. H. Gschweng"'

1. Human CLEC9A antibodies deliver NY-ESO-1 antigen to CD141+ dendritic cells to activate naïve and memory NY-ESO-1-specific CD8+ T cells

Author

Kelly-Anne Masterman, Oscar L Haigh, Kirsteen M Tullett, Ingrid M Leal-Rojas, Carina Walpole, Frances E Pearson, Jonathon Cebon, Christopher Schmidt, Liam O'Brien, Nikita Rosendahl, Ghazal Daraj, Irina Caminschi, Eric H Gschweng, Roger P Hollis, Donald B Kohn, Mireille H Lahoud, and Kristen J Radford

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Background Dendritic cells (DCs) are crucial for the efficacy of cancer vaccines, but current vaccines do not harness the key cDC1 subtype required for effective CD8+ T-cell-mediated tumor immune responses. Vaccine immunogenicity could be enhanced by specific delivery of immunogenic tumor antigens to CD141+ DCs, the human cDC1 equivalent. CD141+ DCs exclusively express the C-type-lectin-like receptor CLEC9A, which is important for the regulation of CD8+ T cell responses. This study developed a new vaccine that harnesses a human anti-CLEC9A antibody to specifically deliver the immunogenic tumor antigen, NY-ESO-1 (New York esophageal squamous cell carcinoma 1), to human CD141+ DCs. The ability of the CLEC9A-NY-ESO-1 antibody to activate NY-ESO-1-specific naïve and memory CD8+ T cells was examined and compared with a vaccine comprised of a human DEC-205-NY-ESO-1 antibody that targets all human DCs.Methods Human anti-CLEC9A, anti-DEC-205 and isotype control IgG4 antibodies were genetically fused to NY-ESO-1 polypeptide. Cross-presentation to NY-ESO-1-epitope-specific CD8+ T cells and reactivity of T cell responses in patients with melanoma were assessed by interferon γ (IFNγ) production following incubation of CD141+ DCs and patient peripheral blood mononuclear cells with targeting antibodies. Humanized mice containing human DC subsets and a repertoire of naïve NY-ESO-1-specific CD8+ T cells were used to investigate naïve T cell priming. T cell effector function was measured by expression of IFNγ, MIP-1β, tumor necrosis factor and CD107a and by lysis of target tumor cells.Results CLEC9A-NY-ESO-1 antibodies (Abs) were effective at mediating delivery and cross-presentation of multiple NY-ESO-1 epitopes by CD141+ DCs for activation of NY-ESO-1-specific CD8+ T cells. When benchmarked to NY-ESO-1 conjugated to an untargeted control antibody or to anti-human DEC-205, CLEC9A-NY-ESO-1 was superior at ex vivo reactivation of NY-ESO-1-specific T cell responses in patients with melanoma. Moreover, CLEC9A-NY-ESO-1 induced priming of naïve NY-ESO-1-specific CD8+ T cells with polyclonal effector function and potent tumor killing capacity in vitro.Conclusions These data advocate human CLEC9A-NY-ESO-1 Ab as an attractive strategy for specific targeting of CD141+ DCs to enhance tumor immunogenicity in NY-ESO-1-expressing malignancies.

Published
2020
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2. Domain-swapped T cell receptors improve the safety of TCR gene therapy

Author

Michael T Bethune, Marvin H Gee, Mario Bunse, Mark S Lee, Eric H Gschweng, Meghana S Pagadala, Jing Zhou, Donghui Cheng, James R Heath, Donald B Kohn, Michael S Kuhns, Wolfgang Uckert, and David Baltimore

Subjects
receptor biogenesis, cancer immunotherapy, protein engineering, autoimmunity, T cell, T cell receptor, Medicine, Science, Biology (General), QH301-705.5
Abstract

T cells engineered to express a tumor-specific αβ T cell receptor (TCR) mediate anti-tumor immunity. However, mispairing of the therapeutic αβ chains with endogenous αβ chains reduces therapeutic TCR surface expression and generates self-reactive TCRs. We report a general strategy to prevent TCR mispairing: swapping constant domains between the α and β chains of a therapeutic TCR. When paired, domain-swapped (ds)TCRs assemble with CD3, express on the cell surface, and mediate antigen-specific T cell responses. By contrast, dsTCR chains mispaired with endogenous chains cannot properly assemble with CD3 or signal, preventing autoimmunity. We validate this approach in cell-based assays and in a mouse model of TCR gene transfer-induced graft-versus-host disease. We also validate a related approach whereby replacement of αβ TCR domains with corresponding γδ TCR domains yields a functional TCR that does not mispair. This work enables the design of safer TCR gene therapies for cancer immunotherapy.

Published
2016
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3. Publisher’s Note: Demonstration of Ignition Radiation Temperatures in Indirect-Drive Inertial Confinement Fusion Hohlraums [Phys. Rev. Lett.106, 085004 (2011)]

Author

B. L. Pepmeier, D. L. Hodtwalker, B. V. Beeman, J. D. Hollis, P. S. Yang, S. A. Silva, M. J. Richardson, J. L. Vaher, K. Gu, B. N. M. Balaoing, J. E. Krammen, P. J. van Arsdall, N. I. Spafford, M. M. Montoya, M. A. Jackson, F. W. Chambers, J. Grippen, M. Neto, P. H. Gschweng, J. D. Moody, C. A. Haynam, S. Huber, A. P. Ludwigsen, E T Alger, G. M. Curnow, J. Watkins, J. C. Ellefson, S. Sailors, B. McHale, L. F. Alvarez, H. Chandrasekaran, T. E. Mills, Cliff Thomas, P. L. Stratton, R. Zacharias, J. D. Hitchcock, P. M. Bell, J. F. Meeker, E. L. Dewald, R. K. Butlin, T. G. Stone, K. P. Youngblood, Mark W. Bowers, M. Runkel, E. Padilla, M. W. Owens, S. S. Alvarez, J. G. Soto, L. J. Atherton, J. McBride, W. A. Reid, M. Y. Mauvais, G. Heestand, O. D. Edwards, S. W. Lane, A. A. Marsh, T. N. Malsbury, S. R. Robison, P. M. Danforth, J. D. Kilkenny, J. A. Baltz, M. J. Dailey, R. C. Montesanti, J. D. Driscoll, B. J. MacGowan, M. K. Shiflett, Donald F. Browning, F. J. Lopez, C. R. Gibson, F. E. Wade, R. Darbee, Mark R. Hermann, B Fishler, Y. Chen, Edward I. Moses, G. A. Kyrala, R. D. Demaret, J. G. Lown, M. D. Magat, S. Azevedo, G. Erbert, R. K. Kirkwood, K. Charron, Harry B. Radousky, R. T. Shelton, M. E. Sheldrick, R. R. Lyons, C. T. Warren, Paul J. Wegner, P. V. Amick, B. Johnson, G. Hermes, K. M. Morriston, G. A. Keating, T. G. Parham, K. S. Andersson, G. Ross, C. H. Ellerbee, D. A. Callahan, A. S. Rivenes, C. B. Foxworthy, M. C. Johnson, R. Miramontes-Ortiz, P. T. Springer, P. Datte, T. Kohut, J. Neumann, A. J. van Prooyen, C. Thai, M. J. Edwards, K. Work, Tilo Döppner, K. D. Pletcher, G. Frieder, D. S. Hey, T. Ma, A. J. Churby, I. L. Maslennikov, M. C. Witte, Siegfried Glenzer, G. J. Mauger, B. E. Smith, Suhas Bhandarkar, S. C. Burkhart, Joseph Ralph, T. J. Clancy, E. Ng, Thomas J. Johnson, K. L. Griffin, Rolf K. Reed, J. Braucht, R. Rinnert, J.M.Fisher, J. M. Di Nicola, N. Lao, A. L. Throop, S. Hunter, R. L. Rampke, Nathan Meezan, D. A. Barker, Otto Landen, Mark Eckart, M. A. Bergonia, K. N. La Fortune, J. R. Kimbrough, T. R. Huppler, R. A. London, G. L. Tietbohl, J. J. Rhodes, Christoph Niemann, Richard Town, W. J. Fabyan, Joseph W. Carlson, K. M. Skulina, G. Pavel, T. W. Phillips, B. D. Cline, R. G. Hartley, R. J. Wallace, T. L. Lee, C. C. Widmayer, Steven H. Langer, L. F. Finnie, J. Morris, G. T. Villanueva, S. W. Kramer, L. K. Smith, J. W. Florio, D. Pigg, J. L. Vickers, A. S. Runtal, F. E. Coffield, D. G. Cocherell, Pamela K. Whitman, S. Le Pape, Michael Stadermann, E. A. Stout, J. Liebman, V. K. Lakamsani, D. K. Bradley, J. A. Borgman, D. G. Mathisen, M. D. Vergino, P. A. Arnold, Kenneth S. Jancaitis, M. D. Rosen, Jeremy Kroll, J. Dugorepec, M. F. Swisher, J. M. Tillman, D. Pendleton, D. E. Speck, E. Mertens, K. King, Q. M. Ngo, G. Bardsley, E. A. Tekle, R. Costa, Robert L. Kauffman, D. T. Boyle, J. E. Hamblen, D. M. Lord, B. L. Lechleiter, M.S.Hutton, T. Fung, J. R. Schaffer, E. M. Giraldez, S. N. Dixit, John R. Celeste, Laurent Divol, L. C. Clowdus, B. K. Young, D. Trummer, H. Gonzales, B. P. Golick, D. T. Maloy, J. P. Holder, Wendi Sweet, S. R. Marshall, G. J. Edwards, Sally Andrews, G. A. Deis, L. J. Bernardez, D. Larson, L. L. Silva, A. McGrew, G Brunton, S. M. Glenn, Alexander Thomas, Jay D. Salmonson, R. E. Olson, C. M. Estes, Wade H. Williams, K. G. Koka, A. I. Barnes, M. A. Vitalich, A. Y. Chakicherla, J. L. Reynolds, B. Haid, J. T. Salmon, L. V. Berzins, O. S. Jones, B. A. Wilson, M. G. Miller, L. M. Kegelmeyer, Mark J. Schmitt, E. J. Bond, D. R. Bopp, G. T. Lau, N. W. Lum, Kevin S. White, J. T. Fink, D. R. Hart, Marilyn Schneider, F. Stanley, D. B. Dobson, F. Barbosa, L. J. Suter, M. Shor, A. V. Hamza, D. L. Hardy, T. McCarville, D. L. Hipple, C. J. Roberts, P. W. Edwards, R. W. Patterson, Ronald B. Robinson, J. B. Tassano, B. S. Raimondi, S. R. Hahn, G. Gururangan, P. C. Dupuy, R. L. Hibbard, J. R. Nelson, D. A. Smauley, M. J. Fischer, J. H. Kamperschroer, G. Holtmeier, Andrew MacPhee, E. A. Williams, P. A. Adams, K. G. Krauter, Jose Milovich, Stephen P. Vernon, L. J. Lagin, G. N. Gawinski, J. S. Taylor, G. Antonini, M. P. Johnston, M. C. Valadez, M. A. Weingart, S. L. Edson, John Kline, S. M. Gross, A. Baron, J. D. Tappero, N. L. Orsi, J. A. Davis, J. Klingmann, N. J. Cahayag, Carlos E. Castro, J. D. Lindl, A. T. Rivera, L. R. Belk, S. L. Kenitzer, J. Duncan, K. E. Burns, A. L. Solomon, R. C. Bettenhausen, B. M. Van Wonterghem, S. P. Rogers, R G Beeler, D. Latray, H. K. Loey, T. M. Pannell, B. Felker, T. Frazier, V. Rekow, P. G. Zapata, A. J. Mackinnon, R. W. Carey, P. S. Cardinale, J. Jackson, John Moody, S. Burns, L. Willis, J. L. Bragg, D. E. Petersen, E. G. Dzenitis, D. R. Jedlovec, J. R. Cox, D. E. Hinkel, J. A. Robinson, John R. Bower, E. O. Vergel de Dios, B. A. Hammel, L. M. Burrows, Daniel H. Kalantar, Klaus Widmann, M. J. Christensen, R. Prasad, A. L. Warrick, K. Wilhelmsen, R. Chapman, O. R. Rodriguez, A. W. Huey, B. L. Olejniczak, G. W. Krauter, S. W. Haan, Claire Bishop, H. Zhang, J. B. Alfonso, J. H. Truong, S. Weaver, K. S. Segraves, S. Sommer, J. C. Bell, Y. Lee, S. Shiromizu, R. Saunders, R. N. Fallejo, K. Piston, J. Wen, R. M. Marquez, K. L. Tribbey, S. A. Gonzales, P. Di Nicola, R. M. Franks, A. Nikroo, G. A. Bowers, J. B. McCloud, K. A. Moreno, Nobuhiko Izumi, S. F. Locke, S. A. Vonhof, E. F. Wilson, M. D. Finney, D. P. Atkinson, Damien Hicks, R. Lowe-Webb, R. A. Sacks, B. Riordan, M. Fedorov, A. B. Langdon, Z. Alherz, D. N. Hulsey, E. K. Krieger, S. J. Cohen, T. M. Schindler, B. Burr, J. S. Merill, C. Powell, Pierre Michel, J. S. Zielinski, M. J. Gonzales, C. Marshall, Richard Berger, C. Chan, J. Li, S. L. Townsend, L. Auyang, F. A. Penko, A. D. Casey, C. Chang, D. L. Brinkerhoff, K. M. Knittel, R. J. Strauser, G. Markham, and M. J. Shaw

Subjects
Nuclear physics, Physics, Ignition system, Hohlraum, law, General Physics and Astronomy, Plasma confinement, Magnetic confinement fusion, Plasma, Atomic physics, Radiation, Inertial confinement fusion, law.invention
Published
2011

4. Demonstration of Ignition Radiation Temperatures in Indirect-Drive Inertial Confinement Fusion Hohlraums

Author

L. V. Berzins, L. M. Kegelmeyer, D. R. Hart, L. J. Suter, M. Shor, Ronald B. Robinson, S. S. Alvarez, G. Gururangan, Robert L. Kauffman, C. T. Warren, R. Darbee, Andrew MacPhee, J. R. Nelson, D. A. Smauley, M. J. Fischer, K. S. Andersson, D. A. Callahan, L. J. Atherton, D. S. Hey, J. D. Kilkenny, T. Ma, J. H. Kamperschroer, T. Frazier, T. J. Clancy, E. A. Williams, P. A. Adams, C. Thai, Laurent Divol, G. J. Edwards, Suhas Bhandarkar, K. Work, M. D. Magat, S. Hunter, Stephen P. Vernon, T. L. Lee, Rolf K. Reed, J.M.Fisher, O. S. Jones, D. Trummer, G. N. Gawinski, G. Antonini, M. P. Johnston, A. J. Mackinnon, M. E. Sheldrick, T. R. Huppler, B. A. Wilson, J. P. Holder, P. L. Stratton, Yiping Chen, J. Jackson, S. Sailors, John Moody, Mark J. Schmitt, L. K. Smith, R. G. Hartley, E. J. Bond, P. Datte, S. Burns, B. McHale, G. Bardsley, D. T. Boyle, D. R. Bopp, E. L. Dewald, J. E. Hamblen, L. Willis, K. G. Krauter, J. R. Schaffer, D. G. Mathisen, M. D. Rosen, J. Morris, M.S.Hutton, G. T. Lau, N. W. Lum, G. Hermes, G. A. Deis, K. N. La Fortune, M. C. Johnson, J. Neumann, C. C. Widmayer, Steven H. Langer, L. F. Finnie, M. C. Witte, K. King, Michael Stadermann, E. A. Stout, M. G. Miller, Wendi Sweet, T. G. Stone, E. A. Tekle, P. M. Danforth, H. Chandrasekaran, D. Larson, M. F. Swisher, J. T. Fink, G. Frieder, L. Bezerides, Kenneth S. Jancaitis, A. L. Throop, B. L. Lechleiter, S. N. Dixit, Kevin S. White, C. Chang, M. K. Shiflett, G. A. Kyrala, F. Stanley, J. Braucht, John Kline, S. M. Gross, A. Baron, R G Beeler, S. Azevedo, R. A. London, T. E. Mills, G Brunton, Marilyn Schneider, M. J. Dailey, R. C. Montesanti, J. Dugorepec, A. J. Churby, I. L. Maslennikov, D. Latray, F. Barbosa, P. A. Arnold, A. A. Marsh, J. J. Rhodes, G. L. Tietbohl, Alexander Thomas, D. B. Dobson, J. M. Tillman, L. L. Silva, G. Erbert, D. A. Barker, R. D. Demaret, J. A. Davis, S. M. Glenn, J. Klingmann, Edward I. Moses, T. M. Pannell, R. T. Shelton, J. M. Di Nicola, N. J. Cahayag, T. Fung, R. L. Rampke, S. Le Pape, Jay D. Salmonson, G. Ross, R. E. Olson, E. Mertens, J. D. Lindl, J. G. Lown, C. M. Estes, A. T. Rivera, Mark W. Bowers, M. Runkel, F. E. Coffield, Wade H. Williams, K. G. Koka, B. A. Hammel, L. M. Burrows, A. S. Rivenes, Daniel H. Kalantar, M. A. Vitalich, M. Y. Mauvais, D. G. Cocherell, J. Grippen, P. V. Amick, B. K. Young, J. G. Soto, A. McGrew, M. J. Edwards, Tilo Döppner, M. J. Christensen, Jeremy Kroll, J. L. Vaher, C. H. Ellerbee, T. N. Malsbury, C. A. Haynam, B. Haid, J. T. Salmon, A. J. van Prooyen, A. L. Warrick, R. Costa, A. V. Hamza, T. G. Parham, C. R. Gibson, S. A. Silva, D. Pendlton, A. W. Huey, P. M. Bell, K. P. Youngblood, B. N. M. Balaoing, Joseph Ralph, R. Rinnert, B Fishler, D. L. Hardy, K. D. Pletcher, J. Liebman, R. K. Butlin, B. Johnson, T. McCarville, L. C. Clowdus, Otto Landen, V. K. Lakamsani, B. P. Golick, F. W. Chambers, D. T. Maloy, D. L. Hipple, C. B. Foxworthy, O. D. Edwards, C. J. Roberts, T. Zaleski, S. C. Burkhart, Thomas J. Johnson, N. Lao, S. R. Marshall, J. A. Baltz, D. E. Speck, R. Miramontes, J. E. Krammen, P. J. van Arsdall, M. A. Bergonia, K. M. Skulina, R. J. Strausser, K. M. Knittel, Siegfried Glenzer, G. J. Mauger, B. E. Smith, Sally Andrews, G. Heestand, P. W. Edwards, E. M. Giraldez, John R. Celeste, N. I. Spafford, R. W. Patterson, J. Watkins, J. B. Tassano, J. C. Ellefson, B. S. Raimondi, Christoph Niemann, M. M. Montoya, M. A. Jackson, T. W. Phillips, H. Gonzales, E. Ng, Mark Eckart, D. M. Lord, S. R. Hahn, L. J. Bernardez, B. D. Cline, A. Forsman, J. W. Florio, D. Pigg, Donald F. Browning, J. L. Vickers, K. M. Morriston, G. A. Keating, G. Pavel, P. C. Dupuy, A. S. Runtal, R. L. Hibbard, P. T. Springer, T. Kohut, B. L. Pepmeier, Richard Town, W. J. Fabyan, S. Huber, A. P. Ludwigsen, G. Holtmeier, D. L. Hodtwalker, M. Neto, P. H. Gschweng, J. D. Moody, K. L. Griffin, B. V. Beeman, J. D. Hollis, E T Alger, G. M. Curnow, P. S. Yang, E. Padilla, M. W. Owens, M. J. Richardson, S. R. Robison, K. Gu, F. J. Lopez, G. Markham, M. J. Shaw, F. E. Wade, R. K. Kirkwood, Pamela K. Whitman, Cliff Thomas, L. F. Alvarez, D. K. Bradley, J. F. Meeker, J. A. Borgman, M. D. Vergino, J. McBride, W. A. Reid, D. E. Petersen, J. S. Taylor, G. T. Villanueva, M. C. Valadez, D. E. Hinkel, M. A. Weingart, K. Charron, S. W. Kramer, R. R. Lyons, S. L. Edson, Klaus Widmann, Q. M. Ngo, H. Zhang, J. B. Alfonso, S. Weaver, J. D. Driscoll, R. M. Marquez, R. M. Franks, A. Nikroo, Mark R. Hermann, R. A. Sacks, Harry B. Radousky, A. B. Langdon, Paul J. Wegner, E. K. Krieger, Pierre Michel, Richard Berger, C. Chan, J. Li, Jose Milovich, J. S. Merill, C. Powell, J. S. Zielinski, L. J. Lagin, S. P. Rogers, J. D. Tappero, N. L. Orsi, S. L. Townsend, L. Auyang, F. A. Penko, V. Rekow, P. G. Zapata, Carlos E. Castro, R. W. Carey, A. D. Casey, K. S. Segraves, D. R. Jedlovec, J. R. Cox, S. Sommer, J. C. Bell, D. L. Brinkerhoff, E. O. Vergel de Dios, G. A. Bowers, R. Zacharias, J. D. Hitchcock, S. W. Lane, R. Prasad, K. A. Moreno, B. J. MacGowan, K. Wilhelmsen, Nobuhiko Izumi, S. F. Locke, R. Chapman, O. R. Rodriguez, S. A. Vonhof, E. F. Wilson, B. L. Olejniczak, G. W. Krauter, R. Lowe-Webb, Nathan Meezan, J. R. Kimbrough, Claire Bishop, D. N. Hulsey, Joseph W. Carlson, R. N. Fallejo, M. J. Gonzalez, L. R. Belk, R. J. Wallace, S. L. Kenitzer, J. Duncan, K. Piston, J. Wen, K. E. Burns, K. L. Tribbey, S. A. Gonzales, J. H. Truong, P. Di Nicola, J. B. McCloud, Y. Lee, S. Shiromizu, T. M. Schindler, B. Burr, R. Saunders, C. Marshall, A. L. Solomon, R. C. Bettenhausen, B. M. Van Wonterghem, H. K. Loey, B. Felker, P. S. Cardinale, M. D. Finney, D. P. Atkinson, Damien Hicks, J. L. Bragg, E. G. Dzenitis, J. A. Robinson, John R. Bower, B. Riordan, S. W. Haan, M. Fedorov, Z. Alherz, S. J. Cohen, A. I. Barnes, A. Y. Chakicherla, and J. L. Reynolds

Subjects
Physics, business.industry, Physics::Optics, General Physics and Astronomy, Implosion, Radiation, Laser, law.invention, Ignition system, Optics, Physics::Plasma Physics, Hohlraum, law, Laser power scaling, Atomic physics, National Ignition Facility, business, Inertial confinement fusion, Astrophysics::Galaxy Astrophysics
Abstract

We demonstrate the hohlraum radiation temperature and symmetry required for ignition-scale inertial confinement fusion capsule implosions. Cryogenic gas-filled hohlraums with 2.2 mm-diameter capsules are heated with unprecedented laser energies of 1.2 MJ delivered by 192 ultraviolet laser beams on the National Ignition Facility. Laser backscatter measurements show that these hohlraums absorb 87% to 91% of the incident laser power resulting in peak radiation temperatures of T(RAD)=300 eV and a symmetric implosion to a 100 μm diameter hot core.

Published
2011

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