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Mesothelin

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https://www.readbyqxmd.com/read/29656320/the-role-of-mesothelin-as-a-diagnostic-and-therapeutic-target-in-pancreatic-ductal-adenocarcinoma-a-comprehensive-review
#1
Federico Nichetti, Antonio Marra, Francesca Corti, Alessandro Guidi, Alessandra Raimondi, Natalie Prinzi, Filippo de Braud, Sara Pusceddu
Mesothelin is a tumor differentiation antigen, which is highly expressed in several solid neoplasms, including pancreatic cancer. Its selective expression on malignant cells and on only a limited number of healthy tissues has made it an interesting candidate for investigation as a diagnostic and prognostic biomarker and as a therapeutic target. Based on a strong preclinical rationale, a number of therapeutic agents targeting mesothelin have entered clinical trials, including immunotoxins, monoclonal antibodies, antibody-drug conjugates, cancer vaccines, and adoptive T cell therapies with chimeric antigen receptors...
April 14, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29652548/ca125-suppresses-amatuximab-immune-effector-function-and-elevated-serum-levels-are-associated-with-reduced-clinical-response-in-first-line-mesothelioma-patients
#2
Nicholas C Nicolaides, Charles Schweizer, Elizabeth B Somers, Wenquan Wang, Shawn Fernando, Erin N Ross, Luigi Grasso, Raffit Hassan, J Bradford Kline
The tumor-shed antigen CA125 has recently been found to bind certain monoclonal antibodies (mAbs) and suppress immune-effector mediated killing through perturbation of the Fc domain with CD16a and CD32a Fc-γ activating receptors on immune-effector cells. Amatuximab is a mAb targeting mesothelin whose mechanism of action utilizes in part antibody-dependent cellular cytotoxicity (ADCC). It is being tested for its therapeutic activity in patients with mesothelioma in combination with first line standard-of-care...
April 13, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29618658/pancreatic-cancer-therapy-with-combined-mesothelin-redirected-chimeric-antigen-receptor-t-cells-and-cytokine-armed-oncolytic-adenoviruses
#3
Keisuke Watanabe, Yanping Luo, Tong Da, Sonia Guedan, Marco Ruella, John Scholler, Brian Keith, Regina M Young, Boris Engels, Suvi Sorsa, Mikko Siurala, Riikka Havunen, Siri Tähtinen, Akseli Hemminki, Carl H June
Pancreatic ductal adenocarcinoma (PDA) is characterized by its highly immunosuppressive tumor microenvironment (TME) that limits T cell infiltration and induces T cell hypofunction. Mesothelin-redirected chimeric antigen receptor T cell (meso-CAR T cell) therapy has shown some efficacy in clinical trials but antitumor efficacy remains modest. We hypothesized that combined meso-CAR T cells with an oncolytic adenovirus expressing TNF-α and IL-2 (Ad5/3-E2F-D24-TNFa-IRES-IL2, or OAd-TNFa-IL2) would improve efficacy...
April 5, 2018: JCI Insight
https://www.readbyqxmd.com/read/29616141/randomised-controlled-trial-to-compare-the-diagnostic-yield-of-positron-emission-tomography-ct-pet-ct-targeted-pleural-biopsy-versus-ct-guided-pleural-biopsy-in-suspected-pleural-malignancy-target-trial
#4
Duneesha de Fonseka, Wendy Underwood, Louise Stadon, Najib Rahman, Anthony Edey, Chris Rogers, Nick A Maskell
Introduction: Pleural malignancy, particularly malignant pleural mesothelioma (MPM) is increasing in incidence due to the long latency period from exposure to asbestos to development of the disease. MPM can be challenging to diagnose. For patients presenting without a pleural effusion, CT-guided biopsy remains the primary choice of biopsy, but the diagnostic sensitivity of this investigation is 70%-75%. Therefore, a proportion of patients will go on to require further biopsies. If the first biopsy is non-diagnostic, the chances of further non-diagnostic biopsies are high in MPM...
2018: BMJ Open Respiratory Research
https://www.readbyqxmd.com/read/29596890/immuno-modulators-enhance-antigen-specific-immunity-and-anti-tumor-effects-of-mesothelin-specific-chimeric-dna-vaccine-through-promoting-dc-maturation
#5
Yu-Li Chen, Ming-Cheng Chang, Ying-Cheng Chiang, Han-Wei Lin, Nai-Yun Sun, Chi-An Chen, Wei-Zen Sun, Wen-Fang Cheng
As a tumor antigen, mesothelin (MSLN) can be identified in various malignancies. MSLN is potential for antigen-specific cancer vaccines. We generated a novel chimeric DNA vaccine using antigen-specific connective tissue growth factor lined with MSLN (CTGF/MSLN). The anti-tumor effects of the CTGF/MSLN DNA vaccine combined with anti-CD40 Ab and toll-like receptor 3 ligand-poly(I:C) were validated in an MSLN-expressing model. CTGF/MSLN DNA with anti-CD40Ab and poly(I:C) vaccinated mice demonstrated potent anti-tumor effects with longer survival and less tumor volumes...
March 26, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29581296/recombinant-immunotoxins-with-albumin-binding-domains-have-long-half-lives-and-high-antitumor-activity
#6
Junxia Wei, Tapan K Bera, Xiu Fen Liu, Qi Zhou, Masanori Onda, Mitchell Ho, Chin-Hsien Tai, Ira Pastan
Recombinant immunotoxins (RITs) are chimeric proteins consisting of a Fv that binds to a cancer cell and a portion of a protein toxin. One of these, Moxetumomab pasudotox, was shown to be effective in treating patients with some leukemias, where the cells are readily accessible to the RIT. However, their short half-life limits their efficacy in solid tumors, because penetration into the tumors is slow. Albumin and agents bound to albumin have a long half-life in the circulation. To increase the time tumor cells are exposed to RITs, we have produced and evaluated variants that contain either an albumin-binding domain (ABD) from Streptococcus or single-domain antibodies from Llama...
March 26, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29574096/measurement-of-indicator-genes-using-global-complementary-dna-cdna-amplification-by-polyadenylic-acid-reverse-transcriptase-polymerase-chain-reaction-poly-a-rt-pcr-a-feasibility-study-using-paired-samples-from-tissue-and-ductal-juice-in-patients-undergoing
#7
Sudip Sanyal, Ajith K Siriwardena, Richard Byers
OBJECTIVES: The aim of this study is to compare gene expression profiles in RNA isolated from pancreatic ductal juice with the RNA expression profiles of the same genes from matched intra-operative tissue samples from pancreatic tumours. METHODS: Intra-operative sampling of pancreatic juice and collection of matched tissue samples was undertaken in patients undergoing pancreatoduodenectomy for clinically suspected pancreatic cancer and a precursor lesion, main-duct intraductal papillary mucinous neoplasm...
March 20, 2018: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/29572256/preclinical-evaluation-of-novel-mesothelin-specific-ligands-for-spect-imaging-of-triple-negative-breast-cancer
#8
Christopher Montemagno, Sandrine Bacot, Mitra Ahmadi, Brigitte Kerfelec, Daniel Baty, Marlene Debiossat, Audrey Soubies, Pascale Perret, Laurent Riou, Daniel Fagret, Alexis Broisat, Catherine Ghezzi
Background: Mesothelin is a cell-surface glycoprotein restricted to mesothelial cells overexpressed in several cancers, including triple negative breast cancers (TNBC) not responding to trastuzumab and hormonal-based therapies. Mesothelin-targeting therapies are currently being developed. However, the identification of patients potentially eligible to such therapeutic strategy remains challenging. The objective of this study was to perform the radiolabeling and pre-clinical evaluation of99m Tc-A1 and99m Tc-C6, two anti-mesothelin single domain antibodies (sdAb)-derived imaging agents...
March 23, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29568387/engineered-t-lymphocytes-eliminate-lung-metastases-in-models-of-pancreatic-cancer
#9
Qiang Sun, Shixin Zhou, Jingjing Zhao, Changwen Deng, Ruidi Teng, Yiding Zhao, Jiajia Chen, Jiebin Dong, Ming Yin, Yun Bai, Hongkui Deng, Jinhua Wen
Pancreatic cancer is known as one of the most lethal cancers in the world. A majority of advanced stage pancreatic cancer patients are diagnosed with distant metastasis and given poor prognoses, calling for a better therapeutic option. Mesothelin, which is overexpressed in pancreatic cancer and other solid tumors, is a potential target for pancreatic cancer immunotherapy. Adoptive transfer of T cells engineered with chimeric antigen receptors (CART cells) was effective for treating CD19-positive leukemia, but it is more difficult for CART cells to eliminate solid tumors...
March 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29567081/activity-of-mesothelin-specific-chimeric-antigen-receptor-t-cells-against-pancreatic-carcinoma-metastases-in-a-phase-1-trial
#10
Gregory L Beatty, Mark H O'Hara, Simon F Lacey, Drew A Torigian, Farzana Nazimuddin, Fang Chen, Irina M Kulikovskaya, Michael C Soulen, Maureen McGarvey, Anne Marie Nelson, Whitney L Gladney, Bruce L Levine, J Joseph Melenhorst, Gabriela Plesa, Carl H June
Pancreatic ductal adenocarcinoma (PDAC) is resistant to T-cell mediated immunotherapy. We engineered T cells to transiently express an mRNA encoding a chimeric antigen receptor (CAR) specific for mesothelin-a protein that is over-expressed by PDAC cells. We performed a phase 1 study to evaluate the safety and efficacy of adoptive cell therapy with autologous mesothelin-specific CAR T cells (CARTmeso cells) in 6 patients with chemotherapy-refractory metastatic PDAC. Patients were given intravenous CARTmeso cells 3 times weekly for 3 weeks...
March 19, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29558951/accurate-control-of-dual-receptor-engineered-t-cell-activity-through-a-bifunctional-anti-angiogenic-peptide
#11
Erhao Zhang, Jieyi Gu, Jianpeng Xue, Chenyu Lin, Chen Liu, Mengwei Li, Jingchao Hao, Sarra Setrerrahmane, Xiaowei Chi, Weiyan Qi, Jialiang Hu, Hanmei Xu
BACKGROUND: Chimeric antigen receptors (CARs) presented on T cell surfaces enable redirection of T cell specificity, which has enormous promise in antitumor therapy. However, excessive activity and poor control over such engineered T cells cause significant safety challenges, such as cytokine release syndrome and organ toxicities. To enhance the specificity and controllable activity of CAR-T cells, we report a novel switchable dual-receptor CAR-engineered T (sdCAR-T) cell and a new switch molecule of FITC-HM-3 bifunctional molecule (FHBM) in this study...
March 20, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29511032/amd3100-augments-the-efficacy-of-mesothelin-targeted-immune-activating-vic-008-in-mesothelioma-by-modulating-intratumoral-immunosuppression
#12
Binghao Li, Yang Zeng, Patrick M Reeves, Chongzhao Ran, Qiuyan Liu, Xiying Qu, Yingying Liang, Zhao Liu, Jianping Yuan, Pierre R Leblanc, Zhaoming Ye, Ann E Sluder, Jeffrey A Gelfand, Timothy A Brauns, Huabiao Chen, Mark C Poznansky
AMD3100 (plerixafor), a CXCR4 antagonist, has been demonstrated to suppress tumor growth and modulate intratumoral T-cell trafficking. However, the effect of AMD3100 on immunomodulation remains elusive. Here, we explored immunomodulation and antitumor efficacy of AMD3100 in combination with a previously developed mesothelin-targeted, immune-activating fusion protein, VIC-008, in two syngeneic, orthotopic models of malignant mesothelioma (MM) in immunocompetent mice. We showed that combination therapy significantly suppressed tumor growth and prolonged animal survival in two mouse models...
March 6, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29507806/biomarkers-in-the-prevention-and-follow-up-of-workers-exposed-to-asbestos
#13
REVIEW
Rudy Foddis, Alessandra Bonotti, Stefano Landi, Poupak Fallahi, Giovanni Guglielmi, Alfonso Cristaudo
Although in most developed countries the use of asbestos is banned, there is still a consistent portion of the world where asbestos extraction, trading and manufacturing of asbestos-made products is largely diffuse. Worldwide, hundreds of millions of people are at risk of developing an asbestos caused disease because of occupational, environmental or domestic exposure. The WHO estimates that asbestos is responsible for more than 100,000 deaths yearly. This scenario has prompted the research on biomarkers potentially useful for early diagnosis, prognosis and preventive programs on exposed population as well...
January 2018: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29507805/serum-mesothelin-and-other-biomarkers-what-have-we-learned-in-the-last-decade
#14
REVIEW
Alfonso Cristaudo, Alessandra Bonotti, Giovanni Guglielmi, Poupak Fallahi, Rudy Foddis
In the last decade there is been much interest in noninvasive, economic and well-accepted diagnostic tests for screening of subjects exposed to asbestos, and in patients with malignant pleuric mesothelioma (MPM) for diagnosis or monitoring response to treatment. Several biomarkers have been suggested as tools for screening and early diagnosis of MPM. Currently, in patients with MPM, have been reported high levels of soluble mesothelin-related peptides (SMRP), plasmatic osteopontin (pOPN), vimentin, fibulin-3 and many others as promising marker for diagnosis, even their use in prevention monitoring is still discussed...
January 2018: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29503128/mesothelin-and-osteopontin-as-circulating-markers-of-diffuse-malignant-peritoneal-mesothelioma-a-preliminary-study
#15
Federica Bruno, Dario Baratti, Antonia Martinetti, Daniele Morelli, Elisa Sottotetti, Chiara Bonini, Marcello Guaglio, Shigeki Kusamura, Marcello Deraco
BACKGROUND: The differential diagnosis between diffuse malignant peritoneal mesothelioma (DMPM) and other peritoneal surface malignancies (PSM) is still challenging. Serum mesothelin and osteopontin are increasingly used as markers of pleural mesothelioma, but their role in DMPM is unclear. We assessed the diagnostic and prognostic values of mesothelin, osteopontin, CEA, CA19.9, CA125, and CA15.3 in DMPM patients. METHODS: Markers were dosed before cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) by enzyme-linked immunosorbent assay (ELISA) in 30 DMPM patients and 14 controls with other PSMs...
February 17, 2018: European Journal of Surgical Oncology
https://www.readbyqxmd.com/read/29479016/asbestos-exposure-biomarkers-in-the-follow-up-of-asbestos-exposed-workers
#16
Valentina Paolucci, Riccardo Romeo, Antonietta Gerardina Sisinni, Giuseppina Scancarello, Luca Volterrani, Maria Antonietta Mazzei, Lucio Barabesi, Pietro Sartorelli
Health surveillance of asbestos exposed workers should be stratified according to the exposure level. Unfortunately there is a lack of information regarding asbestos exposure in many working places and markers of asbestos exposure are often needed. The aim of the study was to assess the reliability of different dose and effect biomarkers in the follow up of asbestos-exposed workers.Mineralogical analysis of bronchoalveolar lavage fluid (BALF) as a biomarker of asbestos fibre burden was performed in a population of 307 male subjects occupationally exposed to asbestos...
February 26, 2018: Industrial Health
https://www.readbyqxmd.com/read/29474384/development-of-improved-therapeutic-mesothelin-based-vaccines-for-pancreatic-cancer
#17
Michael White, Andrew Freistaedter, Gwendolyn J B Jones, Emmanuel Zervos, Rachel L Roper
Pancreatic cancer is the 5th leading cause of cancer deaths, and there are no effective treatments. We developed a poxvirus platform vaccine with improved immunogenicity and inserted the mesothelin gene to create an anti-mesothelin cancer vaccine. Mesothelin expression is mostly restricted to tumors in adult mammals and thus may be a good target for cancer treatment. We show here that the modified vaccinia virus Ankara (MVA) virus expressing mesothelin and the enhanced MVA virus missing the immunosuppressive A35 gene and expressing mesothelin were both safe in mice and were able to induce IFN-gamma secreting T cells in response to mesothelin expressing tumor cells...
2018: PloS One
https://www.readbyqxmd.com/read/29462558/molecular-imaging-of-mesothelin-expressing-ovarian-cancer-with-a-human-and-mouse-cross-reactive-nanobody
#18
Andrew M Prantner, Catherine Yin, Kalika Kamat, Khushboo Sharma, Andrew C Lowenthal, Peter Bawden Madrid, Nathalie Scholler
Mesothelin is an epithelial marker highly expressed at the cell surface of cancer cells from diverse origins, including ovarian and pancreatic adenocarcinomas and mesotheliomas. Previously, we identified and characterized an anti-mesothelin nanobody (NbG3a) for in vitro diagnostic applications. The main goal of this research was to establish the potential of NbG3a as a molecular imaging agent. Site-specific biotinylated NbG3a (bNbG3a) was bound to streptavidin-conjugated reagents for in vitro and in vivo assays...
February 20, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29454314/a-prospective-study-to-investigate-the-role-of-serial-serum-mesothelin-in-monitoring-mesothelioma
#19
Duneesha de Fonseka, David T Arnold, Louise Stadon, Anna Morley, Emma Keenan, Michael Darby, Lynne Armstrong, Paul Virgo, Nick A Maskell
BACKGROUND: Radiological monitoring of malignant pleural mesothelioma (MPM) using modified RECIST criteria is limited by low sensitivity and inter-observer variability. Serial serum mesothelin measurement has shown utility in the assessment of treatment response during chemotherapy but has never been assessed in the longer term follow up of patients. METHODS: This is a single centre study of consecutive patients diagnosed with MPM who received chemotherapy or best supportive care (BSC)...
February 17, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29435293/a-case-of-peritoneal-malignant-mesothelioma-following-radiation-therapy-for-cervical-cancer
#20
Mitsutake Yano, Yuji Ikeda, Tomomi Kato, Mika Sakaki, Sho Sato, Akira Yabuno, Eito Kozawa, Masanori Yasuda
The present study presents a case of peritoneal malignant mesothelioma (PMM) following radiation therapy for cervical cancer. A 34-year-old Japanese woman, without asbestos exposure, was referred to the Department of Gynecologic Oncology, Saitama Medical University International Medical Center due to a cervical mass, and was diagnosed with cervical squamous cell carcinoma (SCC). The serum levels of tumor markers, including SCC antigen and cancer antigen 125 (CA125) were 229.0 ng/ml and 54.4 U/ml, respectively...
February 2018: Molecular and Clinical Oncology
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