المؤلفون: Yi Le, Hong Gao, Joanna Le, Jason L. Hornick, Ronald Bleday, Jon Wee, Zhenglun Zhu

المصدر: iScience, Vol 27, Iss 1, Pp 108731- (2024)

مصطلحات موضوعية: Molecular biology, Immunology, Cancer, Science

الوصف: Summary: Immune suppression within tumor microenvironments (TME) have been implicated in limited efficacy of immune check point inhibitors (ICIs) against solid tumors. Down-regulated VentX expression in tumor associated macrophages (TAMs) underlies phagocytotic anergic phenotype of TAMs, which govern immunological state of TME. In this study, using a tumor immune microenvironment enabling model system (TIME-EMS) of non-small cell lung cancer (NSCLC), we found that PD-1 antibody modestly activates cytotoxic T lymphocytes (CTLs) within the NSCLC-TME but not the status of TIME. We showed that the restoration of VentX expression in TAMs reignites the phagocytotic function of TAMs, which in turn, transforms TIME, activates CTLs in a tumor-specific manner and promotes efficacy of PD-1 antibody against NSCLC but not toxicity on normal lung epithelial cells. Supported by in vivo data on NSG-PDX models of primary human NSCLC, our study revealed potential venues to promote the efficacy of ICI against solid tumors through VentX-based mechanisms.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2589004223028080Test; https://doaj.org/toc/2589-0042Test

الوصول الحر: https://doaj.org/article/ba52bae135fe42ffa501c894e4157e21Test

المؤلفون: Sabina Signoretti, Toni K Choueiri, Cloud Paweletz, Kun Huang, Yufei Wang, Gordon Freeman, Alicia Buck, Gabriella Kastrunes, Marion Grimaud, Atef Fayed, Luann Zerefa, Brandon Piel, Elena Ivanova, Miriam Ficial, Jon Wee, David Barbie, Wayne Marasco, Andras-Gabor Miklosi, Tran Thai, Ming-Ru Wu

المصدر: Journal for ImmunoTherapy of Cancer, Vol 11, Iss Suppl 1 (2023)

مصطلحات موضوعية: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2051-1426Test

الوصول الحر: https://doaj.org/article/1aff22051bf348cc9e22b6ddf72ca71cTest

المؤلفون: Carlos Soriano, Jon Wee

المصدر: Journal of Surgical Oncology. 127:228-232

مصطلحات موضوعية: Oncology, Surgery, General Medicine

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::e8563565cb7f60b8d747f59e9c994258Test
https://doi.org/10.1002/jso.27179Test

المؤلفون: Paul Lawrence Feingold, Darren Bryan, John Kuckelman, Lee Kennedy-Shaffer, Vivian Wang, Ashley Deeb, Jon Wee, Michael Jaklitsch, Margaret Blair Marshall

المصدر: The Annals of Thoracic Surgery.

مصطلحات موضوعية: Pulmonary and Respiratory Medicine, Surgery, Cardiology and Cardiovascular Medicine

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::27417bff91610f27fa0e05d61bf206e4Test
https://doi.org/10.1016/j.athoracsur.2023.05.013Test

المؤلفون: Yufei Wang, Alicia Buck, Michael Lynch, Gabriella Kastrunes, Jae-Won Cho, Marion Grimaud, David Braun, Cecile Razimbaud, Matthew Chang, Atef Fayed, Audrey Apollon, Ze-Hua Li, Luann Zerefa, Brandon Piel, Elena Ivanova, Dennis Bonal, Kristen Jones, Quang-De Nguyen, Zhu Zhu, Kevin Wei, Rebecca Jennings, Miriam Ficial, Maura Aliezah Sticco-Ivins, Sabina Signoretti, Catherine Wu, Toni Choueiri, Jon Wee, Cloud Paweletz, Martin Hemberg, Aedin Culhane, David Barbie, Gordon Freeman, Wayne Marasco

المصدر: Regular and Young Investigator Award Abstracts.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::398fcc4740f0b4a4b7052461ab29e47eTest
https://doi.org/10.1136/jitc-2022-sitc2022.0295Test

المؤلفون: Yufei Wang, Alicia Buck, Gabriella Kastrunes, Rabia Abbas, Michael Lynch, Zhou Zhong, Song-My Hoang, Andras Miklosi, Kun Huang, Jae-Won Cho, Marion Grimaud, Cecile Razimbaud, Matthew Chang, Atef Fayed, Audrey Apollon, Nithyassree Murugan, Ze-Hua Li, Tran Thai, Luann Zerefa, Brandon Piel, Elena Ivanova, Amy Cameron, Quang-De Nguyen, Zhu Zhu, Kevin Wei, Yasmin Nabil Laimon, Aseman Bagheri Sheshdeh, Sabina Signoretti, David A. Braun, Catherine J. Wu, Toni K. Choueiri, Jon Wee, Cloud P. Paweletz, Martin Hemberg, Aedin C. Culhane, David A. Barbie, Gordon J. Freeman, Wayne A. Marasco

المصدر: Cancer Research. 83:886-886

مصطلحات موضوعية: Cancer Research, Oncology

الوصف: Chimeric Antigen Receptor (CAR) T cell therapy is a new type of “living drug” that has proven to be a powerful immunotherapy for hematologic malignancies. To date, there are six CAR-T products approved by the FDA for hematologic malignancies, four targeting CD19, and two targeting B-cell maturation antigen (BCMA). However, this success has not yet been transferred to solid tumors. A major hurdle is the on-target off-tumor toxicities due to the shared expression of target antigen on normal tissues. Carbonic anhydrase IX (CAIX) is highly expressed in clear cell renal cell carcinoma (ccRCC); however, it is also expressed on bile duct at a lower physiological level leading to off-tumor toxicity of CAIX targeted therapies. The first anti-CAIX CAR-T studies, using the 1st generation G250 CAR-T cells plus IL-2 to treat patients with metastatic ccRCC, caused severe liver enzyme abnormalities in the treated patients after CAR-T cell infusions. To understand CAIX expression on tumor and normal tissues, we quantified CAIX expression on ccRCC patient samples and healthy bile duct tissues using direct stochastic optical reconstruction microscopy (dSTORM) which provides single-molecule resolution. Tet-On inducible CAIX expressing cell lines were established to mimic various CAIX densities on normal tissue and tumor samples. Using biolayer interferometry (BLI) and avidity analyzer, we identified a low-affinity, high-avidity anti-CAIX CAR G9. G9 CAR-T cells only kill CAIX high ccRCC tumor cells but not CAIX low normal cholangiocytes, and exhibited a CAIX density dependent response to Tet-On inducible CAIX expressing cell lines. Compared to high-affinity G250 CAR-T cells, G9 showed a better safety profile and a wider therapeutic window. G9 demonstrated a superior ex vivo efficacy on ccRCC patient derived organotypic tumor spheroids (PDOTS) 3D cultures which recapitulate ccRCC patient tumor microenvironment (TME), as well as low toxicity on cholangiocyte derived organotypic spheroids (CDOS). In summary, affinity/avidity fine-tuned CAIX targeted CAR-T cell therapy holds promise to achieve cures of ccRCC by efficaciously killing tumor cells and mitigating on-target off-tumor toxicity on normal tissues. Citation Format: Yufei Wang, Alicia Buck, Gabriella Kastrunes, Rabia Abbas, Michael Lynch, Zhou Zhong, Song-My Hoang, Andras Miklosi, Kun Huang, Jae-Won Cho, Marion Grimaud, Cecile Razimbaud, Matthew Chang, Atef Fayed, Audrey Apollon, Nithyassree Murugan, Ze-Hua Li, Tran Thai, Luann Zerefa, Brandon Piel, Elena Ivanova, Amy Cameron, Quang-De Nguyen, Zhu Zhu, Kevin Wei, Yasmin Nabil Laimon, Aseman Bagheri Sheshdeh, Sabina Signoretti, David A. Braun, Catherine J. Wu, Toni K. Choueiri, Jon Wee, Cloud P. Paweletz, Martin Hemberg, Aedin C. Culhane, David A. Barbie, Gordon J. Freeman, Wayne A. Marasco. Fine-tuned CAIX targeted CAR-T cells exhibit superior efficacy and mitigate on-target off-tumor side effects [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 886.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::6228191cc29b20f75d0890ab5cb46c7fTest
https://doi.org/10.1158/1538-7445.am2023-886Test

المؤلفون: Yufei Wang, Alicia Buck, Marion Grimaud, Aedin Culhane, David Braun, Sreekumar Kodangattil, Cecile Razimbaud, Matthew Chang, Atef Fayed, Audrey Apollon, Gabriella Kastrunes, Luann Zerefa, Brandon Piel, Elena Ivanova, Dennis Bonal, Kristen Jones, Quang-De Nguyen, Zhu Zhu, Kevin Wei, Nicholas Hayden, Madison O'Donnell, Ying Huang, Rebecca Jenning, Miriam Ficial, Maura Aliezah Sticco-Ivins, Sabina Signoretti, Catherine Wu, Toni Choueiri, Jon Wee, Cloud Paweletz, David A. Barbie, Gordon Freeman, Wayne A. Marasco

المصدر: Cancer Research. 82:2814-2814

مصطلحات موضوعية: Cancer Research, Oncology

الوصف: Chimeric Antigen Receptor (CAR) T cell therapy is a new type of “living drug” that has proven to be a powerful, clinically translatable immunotherapy for hematologic malignancies. To date, there are five CAR-T products approved by FDA, four CD19 targeted CAR-T cells, and one targeting B-cell maturation antigen (BCMA). However, this success has not yet been transferred to solid tumors. A major challenge is the immunosuppressive tumor microenvironment (TME). Development of immunotherapies has traditionally been hampered by discrepancies observed between in vitro and in vivo studies and actual clinical trial outcomes. The lack of clinically relevant mouse models for human immunotherapy testing is often seen as the primary cause. Existing clear cell renal cell carcinoma (ccRCC) in vivo models poorly recapitulate the tumor microenvironment (TME). Here we report a ccRCC orthotopic humanized NSG-SGM3 mouse model (ccRCC-hNSG-SGM3) with reconstituted human lymphocytes and bearing human ccRCC skrc-59 cells under the kidney capsule. Human leukocyte antigen (HLA) matched CD34+ human stem cells were used for the humanization to reduce T cell alloreactivity against skrc-59 human ccRCC cells. Tumors were harvested, sorted for CD45+ tumor infiltrating leukocytes (TILs) and single cell RNA sequencing (scRNAseq) was performed to profile the TME in ccRCC-hNSG-SGM3. By comparing to patient data from prospective clinical trials of the anti-PD-1 monoclonal antibody (mAb) nivolumab in advanced ccRCC, the results demonstrated that CD45+ TILs from ccRCC-hNSG-SGM3 reconstitute most CD45+ cell types, including dendritic cells, exhausted CD8 T cells, and regulatory T cells (Tregs), that are observed in advanced ccRCC patient TME. Furthermore, we generated HLA matched Immune Restoring (IR) CAR-T cells which can secrete anti-PD-L1 monoclonal antibody (mAb) locally to restore active antitumor immunity, and we assessed the efficacy and safety of IR CAR-T cells in this model. Anti-CAIX CAR-T cells armored with anti-PD-L1 mAb showed superior efficacy in tumor regression and significantly decreased TIL exhaustion compared to irrelevant CAR or irrelevant payload in this model. In addition, in situ hybridization (ISH) results showed CAR-T cells infiltration in tumor but no CAR-T cells were observed in normal tissues. In summary, the ccRCC-hNSG-SGM3 system is able to model the advanced ccRCC TME and provides a powerful tool for ccRCC TME study and immunotherapy assessment. IR CAR-T cells exhibited superior tumor regression and reversed immunosuppressive TME in humanized mice. Citation Format: Yufei Wang, Alicia Buck, Marion Grimaud, Aedin Culhane, David Braun, Sreekumar Kodangattil, Cecile Razimbaud, Matthew Chang, Atef Fayed, Audrey Apollon, Gabriella Kastrunes, Luann Zerefa, Brandon Piel, Elena Ivanova, Dennis Bonal, Kristen Jones, Quang-De Nguyen, Zhu Zhu, Kevin Wei, Nicholas Hayden, Madison O'Donnell, Ying Huang, Rebecca Jenning, Miriam Ficial, Maura Aliezah Sticco-Ivins, Sabina Signoretti, Catherine Wu, Toni Choueiri, Jon Wee, Cloud Paweletz, David A. Barbie, Gordon Freeman, Wayne A. Marasco. Anti-CAIX Immune Restoring (IR) CAR-T cells display superior antitumor activity and reverse immunosuppressive TME in a humanized ccRCC orthotopic mouse model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2814.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::293a0b3b3bdb92a753d858f3fa1f3e6aTest
https://doi.org/10.1158/1538-7445.am2022-2814Test

المؤلفون: Jon Wee, Nestor Villamizar

المصدر: Evidence-Based Practices in Gastrointestinal, Colorectal and Hepatobiliary Surgery

مصطلحات موضوعية: medicine.medical_specialty, business.industry, General surgery, medicine, Achalasia, medicine.disease, business

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::65760f866d2eacc595a34e7cc8ce8fa5Test
https://doi.org/10.5005/jp/books/13024_14Test

المؤلفون: Lee, Jon Wee

مصطلحات موضوعية: H Social Sciences (General)

وصف الملف: text

العلاقة: http://ir.unimas.my/id/eprint/21473/3/Lee%20Jon%20Wee.pdfTest; Lee, Jon Wee (2005) Organizational climate factors affecting employees' job performance. [Final Year Project Report] (Unpublished)

الإتاحة: http://ir.unimas.my/id/eprint/21473Test/
http://ir.unimas.my/id/eprint/21473/3/Lee%20Jon%20Wee.pdfTest

المؤلفون: Grant Buster, Paul Siratovich, Nicole Taverna, Michael Rossol, Jon Weers, Andrea Blair, Jay Huggins, Christine Siega, Warren Mannington, Alex Urgel, Jonathan Cen, Jaime Quinao, Robbie Watt, John Akerley

المصدر: Energies, Vol 14, Iss 20, p 6852 (2021)

مصطلحات موضوعية: geothermal power plant, systems modeling, machine learning, neural networks, system optimization, digital twins, Technology

الوصف: Geothermal power plants are excellent resources for providing low carbon electricity generation with high reliability. However, many geothermal power plants could realize significant improvements in operational efficiency from the application of improved modeling software. Increased integration of digital twins into geothermal operations will not only enable engineers to better understand the complex interplay of components in larger systems but will also enable enhanced exploration of the operational space with the recent advances in artificial intelligence (AI) and machine learning (ML) tools. Such innovations in geothermal operational analysis have been deterred by several challenges, most notably, the challenge in applying idealized thermodynamic models to imperfect as-built systems with constant degradation of nominal performance. This paper presents GOOML: a new framework for Geothermal Operational Optimization with Machine Learning. By taking a hybrid data-driven thermodynamics approach, GOOML is able to accurately model the real-world performance characteristics of as-built geothermal systems. Further, GOOML can be readily integrated into the larger AI and ML ecosystem for true state-of-the-art optimization. This modeling framework has already been applied to several geothermal power plants and has provided reasonably accurate results in all cases. Therefore, we expect that the GOOML framework can be applied to any geothermal power plant around the world.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1996-1073/14/20/6852Test; https://doaj.org/toc/1996-1073Test

الوصول الحر: https://doaj.org/article/8483f90afec54082840e6a512d4119d4Test