المؤلفون: Catalina Abad, Yossan-Var Tan, Gardenia Cheung-Lau, Hiroko Nobuta, James A. Waschek

المصدر: PLoS ONE, Vol 8, Iss 6 (2013)

مصطلحات موضوعية: Medicine, Science

وصف الملف: electronic resource

العلاقة: http://europepmc.org/articles/PMC3680322Test; https://doaj.org/toc/1932-6203Test

الوصول الحر: https://doaj.org/article/36d6d0a775664b8e84657abb9e9a3e3cTest

المؤلفون: Catalina Abad, Yossan-Var Tan, Gardenia Cheung-Lau, Hiroko Nobuta, James A Waschek

المصدر: PLoS ONE, Vol 7, Iss 5, p e36922 (2012)

مصطلحات موضوعية: Medicine, Science

الوصف: Vasoactive intestinal peptide (VIP) is a pleiotropic neuropeptide with immunomodulatory properties. The administration of this peptide has been shown to have beneficial effects in murine models of inflammatory diseases including septic shock, rheumatoid arthritis, multiple sclerosis (MS) and Crohn's disease. However, the role of the endogenous peptide in inflammatory disease remains obscure because VIP-deficient mice were recently found to exhibit profound resistance in a model of MS. In the present study, we analyzed the response of female VIP deficient (KO) mice to intraperitoneal lipopolysaccharide (LPS) administration. We observed significant resistance to LPS in VIP KO mice, as evidenced by lower mortality and reduced tissue damage. The increased survival was associated with decreased levels of proinflammatory cytokines (TNFα, IL-6 and IL-12) in sera and peritoneal suspensions of these mice. Moreover, the expression of TNFα and IL-6 mRNA was reduced in peritoneal cells, spleens and lungs from LPS-treated VIP KO vs. WT mice, suggesting that the resistance might be mediated by an intrinsic defect in the responsiveness of immune cells to endotoxin. In agreement with this hypothesis, peritoneal cells isolated from VIP KO naive mice produced lower levels of proinflammatory cytokines in response to LPS in vitro. Finally, decreased NF-κB pathway activity in peritoneal cells was observed both in vivo and in vitro, as determined by assay of phosphorylated I-κB. The results demonstrate that female VIP KO mice exhibit resistance to LPS-induced shock, explainable in part by the presence of an intrinsic defect in the responsiveness of inflammatory cells to endotoxin.

وصف الملف: electronic resource

العلاقة: http://europepmc.org/articles/PMC3355097?pdf=renderTest; https://doaj.org/toc/1932-6203Test

الوصول الحر: https://doaj.org/article/a61b0535193043d1a9926f6386fec3e0Test

المؤلفون: Antoni Ribas, Siwen Hu-Lieskovan, Begoña Comin-Anduix, Beata Berent-Maoz, Catherine S. Grasso, Pau Mascaro, Christopher M. Lee, Agustin Vega-Crespo, Paige Krystofinski, Thomas Wohlwender, Gardenia Cheung-Lau, Cristina Puig-Saus, Angel Garcia-Diaz, Jesse M. Zaretsky, Giulia Parisi, Anusha Kalbasi, Katie M. Campbell, Jennifer Tsoi, Ameya S. Champhekar, Gabriel Abril-Rodriguez, Davis Y. Torrejon

الوصف: Mechanism-based strategies to overcome resistance to PD-1 blockade therapy are urgently needed. We developed genetic acquired resistant models of JAK1, JAK2, and B2M loss-of-function mutations by gene knockout in human and murine cell lines. Human melanoma cell lines with JAK1/2 knockout became insensitive to IFN-induced antitumor effects, while B2M knockout was no longer recognized by antigen-specific T cells and hence was resistant to cytotoxicity. All of these mutations led to resistance to anti–PD-1 therapy in vivo. JAK1/2-knockout resistance could be overcome with the activation of innate and adaptive immunity by intratumoral Toll-like receptor 9 agonist administration together with anti–PD-1, mediated by natural killer (NK) and CD8 T cells. B2M-knockout resistance could be overcome by NK-cell and CD4 T-cell activation using the CD122 preferential IL2 agonist bempegaldesleukin. Therefore, mechanistically designed combination therapies can overcome genetic resistance to PD-1 blockade therapy.Significance:The activation of IFN signaling through pattern recognition receptors and the stimulation of NK cells overcome genetic mechanisms of resistance to PD-1 blockade therapy mediated through deficient IFN receptor and antigen presentation pathways. These approaches are being tested in the clinic to improve the antitumor activity of PD-1 blockade therapy.This article is highlighted in the In This Issue feature, p. 1079

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::cdae21e426b8a218be5691b762b2da24Test
https://doi.org/10.1158/2159-8290.c.6547868.v1Test

المؤلفون: Antoni Ribas, Siwen Hu-Lieskovan, Begoña Comin-Anduix, Beata Berent-Maoz, Catherine S. Grasso, Pau Mascaro, Christopher M. Lee, Agustin Vega-Crespo, Paige Krystofinski, Thomas Wohlwender, Gardenia Cheung-Lau, Cristina Puig-Saus, Angel Garcia-Diaz, Jesse M. Zaretsky, Giulia Parisi, Anusha Kalbasi, Katie M. Campbell, Jennifer Tsoi, Ameya S. Champhekar, Gabriel Abril-Rodriguez, Davis Y. Torrejon

الوصف: Supplementary Figures

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::29cf61ebc7ab22767d36e65d96e0d9d3Test
https://doi.org/10.1158/2159-8290.22535462.v1Test

المؤلفون: Antoni Ribas, Arun Singh, Begoña Comin-Anduix, Bartosz Chmielowski, Siwen Hu-Lieskovan, Catherine S. Grasso, Alistair J. Cochran, Anusha Kalbasi, Ignacio Baselga Carretero, Ivan Perez Garcilazo, Mignonette Macabali, Jia Pang, Justin Tran, Paula Cabrera, Paula Kaplan-Lefko, Jennifer Tsoi, Xiaoyan Wang, Rong Rong Huang, Gardenia Cheung-Lau, Beata Berent-Maoz, Theodore S. Nowicki

الوصف: Supplementary Methods

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::653622c89df1c6e55596e1aae11849fcTest
https://doi.org/10.1158/1078-0432.22473227Test

المؤلفون: Antoni Ribas, Arun Singh, Begoña Comin-Anduix, Bartosz Chmielowski, Siwen Hu-Lieskovan, Catherine S. Grasso, Alistair J. Cochran, Anusha Kalbasi, Ignacio Baselga Carretero, Ivan Perez Garcilazo, Mignonette Macabali, Jia Pang, Justin Tran, Paula Cabrera, Paula Kaplan-Lefko, Jennifer Tsoi, Xiaoyan Wang, Rong Rong Huang, Gardenia Cheung-Lau, Beata Berent-Maoz, Theodore S. Nowicki

الوصف: Purpose:Transgenic adoptive cell therapy (ACT) targeting the tumor antigen NY-ESO-1 can be effective for the treatment of sarcoma and melanoma. Preclinical models have shown that this therapy can be improved with the addition of dendritic cell (DC) vaccination and immune checkpoint blockade. We studied the safety, feasibility, and antitumor efficacy of transgenic ACT with DC vaccination, with and without CTLA-4 blockade with ipilimumab.Patients and Methods:Freshly prepared autologous NY-ESO-1–specific T-cell receptor (TCR) transgenic lymphocytes were adoptively transferred together with NY-ESO-1 peptide-pulsed DC vaccination in HLA-A2.1–positive subjects alone (ESO, NCT02070406) or with ipilimumab (INY, NCT01697527) in patients with advanced sarcoma or melanoma.Results:Six patients were enrolled in the ESO cohort, and four were enrolled in the INY cohort. Four out of six patients treated per ESO (66%), and two out of four patients treated per INY (50%) displayed evidence of tumor regression. Peripheral blood reconstitution with NY-ESO-1–specific T cells peaked within 2 weeks of ACT, indicating rapid in vivo expansion. Tracking of transgenic T cells to the tumor sites was demonstrated in on-treatment biopsies via TCR sequencing. Multiparametric mass cytometry of transgenic cells demonstrated shifting of transgenic cells from memory phenotypes to more terminally differentiated effector phenotypes over time.Conclusions:ACT of fresh NY-ESO-1 transgenic T cells prepared via a short ex vivo protocol and given with DC vaccination, with or without ipilimumab, is feasible and results in transient antitumor activity, with no apparent clinical benefit of the addition of ipilimumab. Improvements are needed to maintain tumor responses.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::353b61840473271b7d3fa56ff75f8412Test
https://doi.org/10.1158/1078-0432.c.6528449Test

المؤلفون: Antoni Ribas, Arun Singh, Begoña Comin-Anduix, Bartosz Chmielowski, Siwen Hu-Lieskovan, Catherine S. Grasso, Alistair J. Cochran, Anusha Kalbasi, Ignacio Baselga Carretero, Ivan Perez Garcilazo, Mignonette Macabali, Jia Pang, Justin Tran, Paula Cabrera, Paula Kaplan-Lefko, Jennifer Tsoi, Xiaoyan Wang, Rong Rong Huang, Gardenia Cheung-Lau, Beata Berent-Maoz, Theodore S. Nowicki

الوصف: Supplemental Figure legends for Figures S1-S5

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9837371d070d3859b3ed38b193896a98Test
https://doi.org/10.1158/1078-0432.22473230.v1Test

المؤلفون: Antoni Ribas, Arun Singh, Begoña Comin-Anduix, Bartosz Chmielowski, Siwen Hu-Lieskovan, Catherine S. Grasso, Alistair J. Cochran, Anusha Kalbasi, Ignacio Baselga Carretero, Ivan Perez Garcilazo, Mignonette Macabali, Jia Pang, Justin Tran, Paula Cabrera, Paula Kaplan-Lefko, Jennifer Tsoi, Xiaoyan Wang, Rong Rong Huang, Gardenia Cheung-Lau, Beata Berent-Maoz, Theodore S. Nowicki

الوصف: List of mass cytometry antibodies utilized.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::011f992b93c8c7e1fafd3692af41b409Test
https://doi.org/10.1158/1078-0432.22473224Test

المؤلفون: Beata Berent-Maoz, Ankush Sachdeva, Thinle Chodon, Paula Cabrera, Jonathan W. Said, Allan J. Pantuck, Gardenia Cheung-Lau, Alexandra Drakaki, Izak Faiena, Begoña Comin-Anduix, Paula Kaplan-Lefko, Arie S. Belldegrun, Xiaoyan Wang, Nazy Zomorodian, Karim Chamie, Jia Pang, Adrian Bot, Mignonette H. Macabali

المصدر: Journal of Immunotherapy. 43:273-282

مصطلحات موضوعية: 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Immunology, Cancer Vaccines, Viral vector, 03 medical and health sciences, 0302 clinical medicine, Immune system, Antigens, Neoplasm, Renal cell carcinoma, Internal medicine, medicine, Humans, Immunology and Allergy, Carbonic Anhydrase IX, Adverse effect, Carcinoma, Renal Cell, Pharmacology, Leukopenia, business.industry, Disease Management, Granulocyte-Macrophage Colony-Stimulating Factor, Dendritic Cells, medicine.disease, Kidney Neoplasms, Clear cell renal cell carcinoma, Treatment Outcome, 030104 developmental biology, 030220 oncology & carcinogenesis, Cohort, Immunotherapy, medicine.symptom, business, Progressive disease

الوصف: Expression of carbonic-anhydrase IX (CAIX) in clear cell renal cell carcinoma (RCC) makes it an attractive vaccine target. We developed a fusion-gene construct, granulocyte-macrophage (GM) colony-stimulating factor+CAIX, delivered by an adenoviral vector (Ad) into autologous dendritic cells (DCs) in this phase 1 study. The injected immature DCs were expected to stimulate an antigen-specific immune response against CAIX expressing RCC. Three dose-escalation cohorts (5, 15, and 50×10 cells/administration) were injected intradermally q2wk×3 doses based on a 3+3 design. The primary objective was the safety of the injections. Secondary objectives were immune responses using enzyme-linked immunosorbent spot, a serum biomarker panel, and clinical response. Fifteen patients with metastatic RCC were enrolled, and 9 patients received all 3 doses. No serious adverse events were seen. There were 3 (33%) patients with grade 1 fatigue, 1 of whom subsequently experienced grade 2 fatigue. One patient (11%) experienced grade 1-2 leukopenia. Only 1 patient (11%) experienced grade 2 flu-like symptoms. Of the 9 patients who received treatment, 1 expired of progressive disease, 2 patients were lost to follow-up and 6 patients are alive. Of the 6 patients, 5 have progressive disease, and 1 has completed treatment with stable disease at 27 months follow-up. Immune response measurements appeared more robust in higher dose cohorts, which appeared to be related to patients with stable disease at 3 months. These early data show that autologous immature DC-AdGMCAIX can be safely given to metastatic RCC patients without any serious adverse events with CAIX-specific immune response elicited by the treatment. These preliminary data support further study of Ad-GMCAIX, particularly with combination therapies that may enhance clinical activity.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1bd29c3067175f138603afbabf7d0d65Test
https://doi.org/10.1097/cji.0000000000000336Test

المؤلفون: Ignacio Baselga-Carretero, Davis Y. Torrejon, Beata Berent-Maoz, Gardenia Cheung-Lau, Theodore S. Nowicki, Michael J. Quist, Catherine S. Grasso, Jesse M. Zaretsky, Antoni Ribas, Gabriel Abril-Rodriguez, Egmidio Medina, Alejandro J. Garcia, William Senapedis, Siwen Hu-Lieskovan, Begoña Comin-Anduix, Wei Liu, Anusha Kalbasi, Cun-Yu Wang, Cristina Puig-Saus, Erkan Baloglu, Jennifer Tsoi

المصدر: Nature cancer, vol 1, iss 2
Nature Cancer, vol 1, iss 2

مصطلحات موضوعية: Cancer Research, Beata, Oncology, biology, media_common.quotation_subject, Pd 1 blockade, Art, biology.organism_classification, Humanities, media_common

الوصف: Author(s): Abril-Rodriguez, Gabriel; Torrejon, Davis Y; Liu, Wei; Zaretsky, Jesse M; Nowicki, Theodore S; Tsoi, Jennifer; Puig-Saus, Cristina; Baselga-Carretero, Ignacio; Medina, Egmidio; Quist, Michael J; Garcia, Alejandro J; Senapedis, William; Baloglu, Erkan; Kalbasi, Anusha; Cheung-Lau, Gardenia; Berent-Maoz, Beata; Comin-Anduix, Begona; Hu-Lieskovan, Siwen; Wang, Cun-Yu; Grasso, Catherine S; Ribas, Antoni

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4278294ad790bea5fe522ca263724f65Test
https://escholarship.org/uc/item/7d94f6g3Test