Search

Your search keyword '"Bridgeman, John"' showing total 343 results
Start Over Author "Bridgeman, John"
343 results on '"Bridgeman, John"'

2. High-affinity CD8 variants enhance the sensitivity of pMHCI antigen recognition via low-affinity TCRs

Author

Knezevic, Lea, Wachsmann, Tassilo L.A., Francis, Ore, Dockree, Tamsin, Bridgeman, John S., Wouters, Anne, de Wet, Ben, Cole, David K., Clement, Mathew, McLaren, James E., Gostick, Emma, Ladell, Kristin, Llewellyn-Lacey, Sian, Price, David A., van den Berg, Hugo A., Tabi, Zsuzsanna, Sessions, Richard B., Heemskerk, Mirjam H.M., and Wooldridge, Linda

Published
2023
Full Text
View/download PDF

9. Signaling via a CD28/CD40 chimeric costimulatory antigen receptor (CoStAR™), targeting folate receptor alpha, enhances T cell activity and augments tumor reactivity of tumor infiltrating lymphocytes

Author

Kalaitsidou, Milena, primary, Moon, Owen R., additional, Sykorova, Martina, additional, Bao, Leyuan, additional, Qu, Yun, additional, Sukumaran, Sujita, additional, Valentine, Michael, additional, Zhou, Xingliang, additional, Pandey, Veethika, additional, Foos, Kay, additional, Medvedev, Sergey, additional, Powell Jr, Daniel J., additional, Udyavar, Akshata, additional, Gschweng, Eric, additional, Rodriguez, Ruben, additional, Dudley, Mark E., additional, Hawkins, Robert E., additional, Kueberuwa, Gray, additional, and Bridgeman, John S., additional

Published
2023
Full Text
View/download PDF

12. The molecular and cellular function of gene-modified T-cells

Author

Bridgeman, John Stephen

Subjects
616.079
Abstract

Chimeric Immune Receptors (CIR) consisting of a carcinoembryonic antigen (CEA)specific single chain antibody fragment (scFv), fused to the CD3s signalling chain from the T-cell receptor (TCR), induce T-cell activation on CEA ligation. The study sought to investigate some of the structural aspects of CIRs with the objective of potentially optimising CIR function. Analysis of several model systems identified Jurkat T-cells as a useful model for assessing CIR-mediated responses to antigen. CIR-expressing Jurkat T-cells demonstrated a dose-dependent increase in CD69 expression in response to CEA. Jurkat T-cells expressing a CIR with the wild-type CD3s transmembrane domain exhibited a significantly higher surface expression of the TCR associated CD3e than cells expressing receptors with any other transmembrane domain. This upregulation of TCR-associated but not TCR-non associated receptors was abrogated by a transmembrane C2G mutation, which effectively prevented dimerisation, or by replacing the transmembrane domain with a heterologous non-dimerising domain. The concentration of CEA required for 50% maximal CD69 expression (ECso) was also significantly increased by both of these modifications. Moving the disulphide bridge to the extracellular domain, but not any other position in the transmembrane domain, permitted redimerisation and partially restored optimal receptor function. This difference in function may be attributed to TCR interactions as wild-type dimeric but not monomeric receptors, as well as inducing an upregulation in TCR complexes in Jurkat T-cells, could also reconstitute TCR expression in CD3s deficient MA5.8 cells. Potential TCR-CIR interactions were further investigated by mutational analysis to the charged transmembrane D6 residue responsible for wild-type CD3s-TCR interactions. Conservative D6N/E/Q mutations permitted dimerisation but significantly impacted on receptor efficiency; however, non-conservative D6K mutations affected receptor dimerisation and had a more severe impact on receptor function. This knowledge obtained from this study was applied to clone a novel CD28-fusion receptor containing the CD3s transmembrane domain with analysis in Jurkat T-cells demonstrating this CIR had a significantly lower ECso than existing CD28-fusion receptors containing the CD28 transmembrane domain. The second aim of this study was to investigate the role of CD2 as a novel costimulatory module. scFv.CD2.CD3s and scFv.CD28.CD2.CD3s activated Jurkat T-cells more efficiently than scFv.CD28.CD3s. However, in primary human T-cells only scFv.CD2.CD3s expressed at levels to observe functional responses. In these cells CD2 costimulation induced higher IFNy secretion than CD28 costimulation. In summary the report highlights the importance of the CD3s transmembrane domain in optimal CIR function and demonstrates the potential for CD2-based CIRs for future clinical trials.

Published
2008

19. ADAM17-dependent proteolysis of L-selectin promotes early clonal expansion of cytotoxic T cells

Author

Mohammed, Rebar N., Wehenkel, Sophie C., Galkina, Elena V., Yates, Emma-Kate, Preece, Graham, Newman, Andrew, Watson, H. Angharad, Ohme, Julia, Bridgeman, John S., Durairaj, Ruban R. P., Moon, Owen R., Ladell, Kristin, Miners, Kelly L., Dolton, Garry, Troeberg, Linda, Kashiwagi, Masahide, Murphy, Gillian, Nagase, Hideaki, Price, David A., Matthews, R. James, Knäuper, Vera, and Ager, Ann

Published
2019
Full Text
View/download PDF

22. 282 Anti-folate receptor alpha (FRα) costimulatory antigen receptor (CoStAR) improves T-cell function across physiologically relevant ranges of FRα expression and T-cell receptor (TCR) affinities

Author

Sykorova, Martina, primary, Mojadidi, Michelle, additional, Bao, Leyuan, additional, Gschweng, Eric, additional, Kalaitsidou, Milena, additional, Kueberuwa, Gray, additional, Zhou, Xingliang, additional, Alvarez-Rodríguez, Rubén, additional, and Bridgeman, John, additional

Published
2022
Full Text
View/download PDF

27. Clinical feasibility and treatment outcomes with nonselected autologous tumor-infiltrating lymphocyte therapy in patients with advanced cutaneous melanoma

Author

Pillai, Manon, Jiang, Yizhou, Lorigan, Paul C, Thistlethwaite, Fiona C, Thomas, Martine, Kirillova, Natalia, Bridgeman, John S, Kueberuwa, Gray, Biswas, Sunetra, Velazquez, Peter, Chonzi, David, Guest, Ryan D, Roberts, Zachary J, and Hawkins, Robert E

Subjects
Original Article
Abstract

Nonselected autologous tumor-infiltrating lymphocytes (TILs) may provide advantages over other treatments for solid tumors, including checkpoint inhibitor-refractory melanoma. This retrospective analysis reports a single-center experience of nonselected autologous TILs derived from digested tumors for compassionate use treatment of advanced cutaneous melanoma, including after programmed cell death protein 1 (PD-1) inhibition. Patients with histologically confirmed metastatic cutaneous melanoma and no standard-of-care treatment options underwent tumor resection for TIL product manufacturing. Patients received lymphodepleting chemotherapy with cyclophosphamide for 2 days and fludarabine for 5 days, followed by a single TIL infusion and post-TIL high-dose interleukin (IL)-2. Safety assessments included clinically significant adverse events (AEs). Efficacy assessments included overall response rate (ORR), complete response (CR) rate, disease control rate (DCR), and overall survival. Between October 2011 and August 2019, 21 patients underwent treatment (median follow-up time, 52.2 months from TIL infusion). Among all treated patients, median age was 45 years, median number of disease sites was 4, 100% had M1c or M1d disease, and 90% received prior checkpoint inhibitor. Twelve patients received TILs after prior PD-1 inhibition. The safety profile among all treated patients and the prior PD-1 inhibitor subgroup was generally consistent with lymphodepletion and high-dose IL-2. No treatment-related deaths occurred. Among all patients, the ORR was 67%, CR rate was 19%, and the DCR was 86%, which was consistent with that observed in the prior PD-1 inhibitor subgroup (58%, 8%, and 75%, respectively). Median overall survival in all treated patients and the prior PD-1 inhibitor subgroup was 21.3 months. In total, 5 patients (24%) had durable ongoing responses (>30 months post-TIL infusion) at data cutoff, and all patients who achieved CR remained alive and disease free. To further illustrate how TIL therapy may integrate into established treatment paradigms, several case studies of patients treated in this series were included. Overall, these data demonstrate that manufacturing of nonselected autologous TILs from tumor digests is feasible and resulted in high rates of durable response in poor-risk patient populations, which may address significant unmet medical need.

Published
2022

30. Antitumor activity of T cells expressing a novel anti-folate receptor alpha (FOLR1) costimulatory antigen receptor (CoStAR) in a human xenograft murine solid tumor model and implications for in-human studies.

Author

Moon, Owen R., primary, Qu, Yun, additional, King, Michael G., additional, Mojadidi, Michelle, additional, Chauvin-Fleurence, Cynthia, additional, Yarka, Clare, additional, Evans, Alicia, additional, Zhou, Xingliang, additional, Katopodi, Tania (Theoni), additional, Udyavar, Akshata, additional, Bridgeman, John S., additional, Kueberuwa, Gray, additional, and Alvarez-Rodríguez, Rubén, additional

Published
2022
Full Text
View/download PDF

31. RAC2, AEP, and ICAM1 expression are associated with CNS disease in a mouse model of pre-B childhood acute lymphoblastic leukemia

Author

Holland, Mark, Castro, Fernanda V., Alexander, Seema, Smith, Duncan, Liu, Jizhong, Walker, Michael, Bitton, Danny, Mulryan, Kate, Ashton, Garry, Blaylock, Morgan, Bagley, Steve, Connolly, Yvonne, Bridgeman, John, Miller, Crispin, Krishnan, Shekhar, Dempsey, Clare, Masurekar, Ashish, Stern, Peter, Whetton, Anthony, and Saha, Vaskar

Published
2011
Full Text
View/download PDF

33. 199 Potent T cell costimulation mediated by a novel costimulatory antigen receptor (CoStAR) with dual CD28/CD40 signaling domains to improve adoptive cell therapies

Author

Sykorova, Martina, primary, Bao, Leyuan, additional, Chauvin-Fleurence, Cynthia, additional, Kalaitsidou, Milena, additional, Brocq, Michelle Le, additional, Hawkins, Robert, additional, Kueberuwa, Gray, additional, Bridgeman, John, additional, and Alvarez-Rodríguez, Rubén, additional

Published
2021
Full Text
View/download PDF

34. 177 Treatment outcomes with unselected autologous tumor infiltrating lymphocytes in patients with checkpoint inhibition–refractory advanced cutaneous melanoma

Author

Hawkins, Robert, primary, Jiang, Yizhou, additional, Lorigan, Paul C, additional, Thistlethwaite, Fiona C, additional, Pillai, Manon, additional, Thomas, Martine, additional, Kirillova, Natalia, additional, Bridgeman, John S, additional, Kueberuwa, Gray, additional, Guest, Ryan D, additional, and Roberts, Zachary J, additional

Published
2021
Full Text
View/download PDF

38. Abstract LB150: Clinical Feasibility and Treatment Outcomes with Unselected Autologous Tumor Infiltrating Lymphocyte Therapy in Patients with Advanced Cutaneous Melanoma

Author

Hawkins, Robert E., primary, Jiang, Yizhou, additional, Lorigan, Paul C., additional, Thistlethwaite, Fiona C., additional, Pillai, Manon, additional, Thomas, Martine, additional, Kirilova, Natalia, additional, Bridgeman, John S., additional, Kueberuwa, Gray, additional, Guest, Ryan S., additional, and Roberts, Zachary J., additional

Published
2021
Full Text
View/download PDF

39. JAPAN'S MODERN SECURITY POLICY TRAJECTORY: POST–COLD WAR EXPLANATIONS AND FUTURE IMPLICATIONS

Author

Weiner, Robert J., Huntley, Wade L., National Security Affairs (NSA), Bridgeman, John T., Weiner, Robert J., Huntley, Wade L., National Security Affairs (NSA), and Bridgeman, John T.

Abstract

This thesis explores three aspects of post–Cold War Japanese security policy development. First, what significant security policy changes have occurred between 1989 and 2020? Second, what were the underlying factors that created the observed policy outcome? Third, how durable do those factors appear to be in 2020 and beyond? This thesis concludes with an assessment of Japan's probable future security policy trajectory, based upon the answers to the three foregoing questions. In seeking to answer the above questions, this thesis draws four primary conclusions. First, that Japan has maintained a consistent, but limited, security policy trajectory toward militarization over the observed period from 1989–2020. Second, that the observed trajectory is being driven by an interaction between external factors (China threat, North Korea threat, U.S. force presence, and U.S. diplomacy) and internal factors (antiwar norms, suspicion of revisionists, single-party dominance, and prime minister preferences). Third, that the factors driving Japan’s security policy trajectory toward militarization are currently durable in both vector and degree, while the factors resisting further militarization are situationally malleable. Fourth, and finally, that Japan is likely to remain on a long-term trajectory toward further militarization, in which Japanese technological and legal capability for use of force will continue to expand., http://archive.org/details/japansmodernsecu1094566595, Lieutenant, United States Navy, Approved for public release. distribution is unlimited

Published
2021

44. Temporal and spatial variations in bulk chlorine decay within a water supply system

Author

Courtis, Benjamin J., West, John R., and Bridgeman, John

Subjects
Water pollution -- United States, Water pollution -- Control, Chlorine -- Environmental aspects, Chlorine -- Health aspects, Chlorine -- Complications and side effects, Water -- Purification, Water -- Economic aspects, Water -- Standards, Water -- Complications and side effects, Water -- Distribution, Engineering and manufacturing industries, Environmental issues
Abstract

Modern water treatment must maintain an acceptable balance between the microbial safety of potable water supply, the costs of treatment, and the formation of potentially harmful disinfection by-products (DBPs). In order to achieve the optimum balance, it is essential to understand and predict both the formation of DBP and the decay of chlorine, in relation to source water, treatment processes, storage, and supply. Reported herein are new data which demonstrate the lack of durability, precision, and accuracy associated with earlier empirical chlorine decay rate equations. This work develops an improved methodology for the prediction of variation in chlorine decay rates in distribution systems enabling practical, cost-effective prediction of the effects of both seasonal variations and management interventions on chlorine levels at treatment works and in distribution systems. DOI: 10.1061/(ASCE)0733-9372(2009)135:3(147) CE Database subject headings: Kinetics; Regression models; Water distribution systems; Water quality; Water sampling; Chlorine.

Published
2009

46. JAPAN'S MODERN SECURITY POLICY TRAJECTORY: POST–COLD WAR EXPLANATIONS AND FUTURE IMPLICATIONS

Author

Bridgeman, John T., Weiner, Robert J., Huntley, Wade L., and National Security Affairs (NSA)

Subjects
Japan, capability, trajectory, internal, factors, security, force, external, policy
Abstract

This thesis explores three aspects of post–Cold War Japanese security policy development. First, what significant security policy changes have occurred between 1989 and 2020? Second, what were the underlying factors that created the observed policy outcome? Third, how durable do those factors appear to be in 2020 and beyond? This thesis concludes with an assessment of Japan's probable future security policy trajectory, based upon the answers to the three foregoing questions. In seeking to answer the above questions, this thesis draws four primary conclusions. First, that Japan has maintained a consistent, but limited, security policy trajectory toward militarization over the observed period from 1989–2020. Second, that the observed trajectory is being driven by an interaction between external factors (China threat, North Korea threat, U.S. force presence, and U.S. diplomacy) and internal factors (antiwar norms, suspicion of revisionists, single-party dominance, and prime minister preferences). Third, that the factors driving Japan’s security policy trajectory toward militarization are currently durable in both vector and degree, while the factors resisting further militarization are situationally malleable. Fourth, and finally, that Japan is likely to remain on a long-term trajectory toward further militarization, in which Japanese technological and legal capability for use of force will continue to expand. http://archive.org/details/japansmodernsecu1094566595 Lieutenant, United States Navy Approved for public release. distribution is unlimited

Published
2020

47. JAPAN'S MODERN SECURITY POLICY TRAJECTORY: POST–COLD WAR EXPLANATIONS AND FUTURE IMPLICATIONS

Author

Weiner, Robert J., Huntley, Wade L., National Security Affairs (NSA), Bridgeman, John T., Weiner, Robert J., Huntley, Wade L., National Security Affairs (NSA), and Bridgeman, John T.

Abstract

This thesis explores three aspects of post–Cold War Japanese security policy development. First, what significant security policy changes have occurred between 1989 and 2020? Second, what were the underlying factors that created the observed policy outcome? Third, how durable do those factors appear to be in 2020 and beyond? This thesis concludes with an assessment of Japan's probable future security policy trajectory, based upon the answers to the three foregoing questions. In seeking to answer the above questions, this thesis draws four primary conclusions. First, that Japan has maintained a consistent, but limited, security policy trajectory toward militarization over the observed period from 1989–2020. Second, that the observed trajectory is being driven by an interaction between external factors (China threat, North Korea threat, U.S. force presence, and U.S. diplomacy) and internal factors (antiwar norms, suspicion of revisionists, single-party dominance, and prime minister preferences). Third, that the factors driving Japan’s security policy trajectory toward militarization are currently durable in both vector and degree, while the factors resisting further militarization are situationally malleable. Fourth, and finally, that Japan is likely to remain on a long-term trajectory toward further militarization, in which Japanese technological and legal capability for use of force will continue to expand.

Published
2020

48. A Molecular Basis for the Control of Preimmune Escape Variants by HIV-Specific CD8+ T Cells

Author

Ladell, Kristin, Hashimoto, Masao, Iglesias, Maria Candela, Wilmann, Pascal G., McLaren, James E., Gras, Stéphanie, Chikata, Takayuki, Kuse, Nozomi, Fastenackels, Solène, Gostick, Emma, Bridgeman, John S., Venturi, Vanessa, Arkoub, Zaïna Aït, Agut, Henri, van Bockel, David J., Almeida, Jorge R., Douek, Daniel C., Meyer, Laurence, Venet, Alain, Takiguchi, Masafumi, Rossjohn, Jamie, Price, David A., and Appay, Victor

Published
2013
Full Text
View/download PDF

49. Understanding metal concentration and speciation in motorway runoff.

Author

Zakharova, Julia, Pouran, Hamid, Bridgeman, John, Wheatley, Andrew, and Arif, Mohammed

Subjects
RUNOFF, SEWAGE disposal plants, EXPRESS highways, SEWAGE purification, ROAD maintenance, IRON, PHOSPHORUS in water, TRACE metals
Abstract

Although highway runoff has historically been extensively studied, the increasing complexity of stormwater management means that there are still significant gaps regarding the reduction of soluble metals. The work reported in this paper addresses these challenges by analysing the presence and behaviour of iron, copper and zinc in runoff from junction 24 of the M1 motorway in the UK (peak traffic flow: 30,000 vehicles per hour) and comparing it with other urban sources of metals found in the same catchment (a local brook and sewage treatment works). The sampling site included an interceptor and a treatment lagoon and the event monitoring indicated a trend by which the metals did not change their concentration or particulate soluble proportion immediately, hence showing that pre- and post-storm conditions are important factors when analysing the solubility of metals and their behaviour. The data provided further evidence of the important influence of storm characteristics on metal concentrations in highway runoff, in particular the effects of an antecedent dry weather period (ADWP). In addition, this study also helped us to better understand how the release of sodium the application of de-icer for road maintenance in winter affects the availability of zinc. [ABSTRACT FROM AUTHOR]

Published
2022
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results