keyword
https://read.qxmd.com/read/38482238/regional-delivery-of-mesothelin-targeted-chimeric-antigen-receptor-t-cell-effectively-and-safely-targets-colorectal-cancer-liver-metastases-in-mice
#1
JOURNAL ARTICLE
Xin Zhou, Minjie Yang, Jiaze Yu, Jingwen Tan, Nan Xu, Yongjie Zhou, Wen Zhang, Jingqin Ma, Zihan Zhang, Alex Friedlaender, Justin Taylor, Lei Yu, Zhiping Yan
BACKGROUND: Liver metastasis is the major cause of colorectal cancer related death. Mesothelin (MSLN)-targeted chimeric antigen receptor (CAR) T-cell therapy has been illustrated effective and safe through regional delivery of breast cancer, ovarian cancer and malignant mesothelioma tumors. Herein, we investigated the safety, efficacy, and immune microenvironment of regional delivery of MSLN (CAR) T-cell in the treatment of colorectal carcinoma liver metastases (CRLM). METHODS: Second-generation MSLN CAR T-cells were administered by portal vein (PV) or caudal vein (CV, systemic administration) delivery in an orthotopic MSLN+ CRLM nonobese diabetic (NOD)/severe combined immunodeficient (SCID)/γc-/- (NSG) mouse model...
February 29, 2024: Journal of Gastrointestinal Oncology
https://read.qxmd.com/read/38475830/car-t-cells-and-t-cells-phenotype-and-function-are-impacted-by-glucocorticoid-exposure-with-different-magnitude
#2
JOURNAL ARTICLE
Thomas Poiret, Sara Vikberg, Esther Schoutrop, Jonas Mattsson, Isabelle Magalhaes
BACKGROUND: Chimeric antigen receptor (CAR) T cell therapy is associated with high risk of adverse events. Glucocorticoids (GCs) are cornerstone in the management of high-grade cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Given the potentially deleterious effects of GCs on CAR T cells anti-tumor activity, increasing our understanding of GCs impact on CAR T cells is crucial. METHODS: Using several CAR T cells i...
March 12, 2024: Journal of Translational Medicine
https://read.qxmd.com/read/38349311/mesothelin-antigen-density-influences-anti-mesothelin-chimeric-antigen-receptor-t-cell-cytotoxicity
#3
JOURNAL ARTICLE
Gerard J Chu, Charles G Bailey, Rajini Nagarajah, Oliver Liang, Cynthia Metierre, Sharon M Sagnella, Laura Castelletti, Dannel Yeo, Stephen Adelstein, John E J Rasko
BACKGROUND AIMS: Several anti-mesothelin (MSLN) chimeric antigen receptor (CAR) T cells are in phase 1/2 clinical trials to treat solid-organ malignancies. The effect of MSLN antigen density on MSLN CAR cytotoxicity against tumor cells has not been examined previously, nor are there data regarding the effect of agents that increase MSLN antigen density on anti-MSLN CAR T cell efficacy. METHODS: MSLN antigen density was measured on a panel of pancreatic cancer and mesothelioma cell lines by flow cytometry...
February 13, 2024: Cytotherapy
https://read.qxmd.com/read/38319303/early-immune-remodeling-steers-clinical-response-to-frontline-chemoimmunotherapy-in-advanced-gastric-cancer
#4
JOURNAL ARTICLE
Minae An, Arnav Mehta, Byung Hoon Min, You Jeong Heo, Samuel J Wright, Milan Parikh, Lynn Bi, Hyuk Lee, Tae Jun Kim, Song-Yi Lee, Jeonghyeon Moon, Ryan J Park, Matthew R Strickland, Woong-Yang Park, Won Ki Kang, Kyoung-Mee Kim, Seung Tae Kim, Samuel J Klempner, Jeeyun Lee
Adding anti-PD1 to 5-FU/platinum improves survival in some advanced gastroesophageal adenocarcinomas (GEA). To understand the effects of chemotherapy and immunotherapy we conducted a phase II frontline trial (n = 47) sequentially adding pembrolizumab to 5-FU/platinum in advanced GEA. Using serial biopsy of the primary tumor at baseline, after one cycle of 5-FU/platinum, and after the addition of pembrolizumab we transcriptionally profiled 358,067 single cells to identify evolving multicellular TME networks...
February 6, 2024: Cancer Discovery
https://read.qxmd.com/read/38269255/specific-targeting-of-mesothelin-expressing-malignant-cells-using-nanobody-functionalized-magneto-fluorescent-nanoassemblies
#5
JOURNAL ARTICLE
Tina Briolay, Judith Fresquet, Damien Meyer, Brigitte Kerfelec, Patrick Chames, Eléna Ishow, Christophe Blanquart
INTRODUCTION: Most current anti-cancer therapies are associated with major side effects due to a lack of tumor specificity. Appropriate vectorization of drugs using engineered nanovectors is known to increase local concentration of therapeutic molecules in tumors while minimizing their side effects. Mesothelin (MSLN) is a well-known tumor associated antigen overexpressed in many malignancies, in particular in malignant pleural mesothelioma (MPM), and various MSLN-targeting anticancer therapies are currently evaluated in preclinical and clinical assays...
2024: International Journal of Nanomedicine
https://read.qxmd.com/read/38234761/mesothelin-expression-correlates-with-elevated-inhibitory-immune-activity-in-patients-with-colorectal-cancer
#6
Midhun Malla, Sachin Kumar Deshkmukh, Sharon Wu, Timothy Samec, Dane Olevian, Reima Naili, El-Rayes Bassel, Joanne Xiu, Alex Farrell, Heinz-Josef Lenz, Emil Lou, Sanjay Goel, David Spetzler, Richard M Goldberg, Lori Hazlehurst
The expression of the protein Mesothelin ( MSLN ) is highly variable in several malignancies including colorectal cancer (CRC) and high levels are associated with aggressive clinicopathological features and worse patient survival. CRC is both a common and deadly cancer; being the third most common in incidence and second most common cause of cancer related death. While systemic therapy remains the primary therapeutic option for most patients with stage IV (metastatic; m) CRC, their disease eventually becomes treatment refractory, and 85% succumb within 5 years...
December 28, 2023: Research Square
https://read.qxmd.com/read/38227666/tumor-resistance-to-anti-mesothelin-car-t-cells-caused-by-binding-to-shed-mesothelin-is-overcome-by-targeting-a-juxtamembrane-epitope
#7
JOURNAL ARTICLE
X F Liu, M Onda, J Schlomer, L Bassel, S Kozlov, C-H Tai, Q Zhou, W Liu, H-E Tsao, R Hassan, M Ho, I Pastan
Despite many clinical trials, CAR-T cells are not yet approved for human solid tumor therapy. One popular target is mesothelin (MSLN) which is highly expressed on the surface of about 30% of cancers including mesothelioma and cancers of the ovary, pancreas, and lung. MSLN is shed by proteases that cleave near the C terminus, leaving a short peptide attached to the cell. Most anti-MSLN antibodies bind to shed MSLN, which can prevent their binding to target cells. To overcome this limitation, we developed an antibody (15B6) that binds next to the membrane at the protease-sensitive region, does not bind to shed MSLN, and makes CAR-T cells that have much higher anti-tumor activity than a CAR-T that binds to shed MSLN...
January 23, 2024: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/38163173/proteomic-profiling-identifies-biomarkers-of-covid-19-severity
#8
JOURNAL ARTICLE
Noa C Harriott, Amy L Ryan
SARS-CoV-2 infection remains a major public health concern, particularly for the aged and those individuals with co-morbidities at risk for developing severe COVID-19. Understanding the pathogenesis and biomarkers associated with responses to SARS-CoV-2 infection remain critical components in developing effective therapeutic approaches, especially in cases of severe and long-COVID-19. In this study blood plasma protein expression was compared in subjects with mild, moderate, and severe COVID-19 disease. Evaluation of an inflammatory protein panel confirms upregulation of proteins including TNFβ, IL-6, IL-8, IL-12, already associated with severe cytokine storm and progression to severe COVID-19...
January 15, 2024: Heliyon
https://read.qxmd.com/read/38123198/-killing-effect-of-anti-msln-icar-nk-cells-derived-from-induced-pluripotent-stem-cells-on-ovarian-epithelial-cancer-cells
#9
JOURNAL ARTICLE
R J Fan, Y F Zhang, Y Y Wang, Y Wang, Wenxin Zheng
Objective: To investigate the cytotoxic effects of induced pluripotent stem (iPS) cells of anti-mesothelin (MSLN)-chimeric antigen receptor natural killer (CAR-NK) cells (anti-MSLN-iCAR-NK cells) on ovarian epithelial cancer cells. Methods: Twenty cases of ovarian cancer patients who underwent surgical treatment at Henan Provincial People's Hospital from September 2020 to September 2021 were collected, and 20 cases of normal ovarian tissues resected during the same period due to other benign diseases were also collected...
December 25, 2023: Zhonghua Fu Chan Ke za Zhi
https://read.qxmd.com/read/38091375/m9657-is-a-bispecific-tumor-targeted-anti-cd137-agonist-that-induces-msln-dependent-antitumor-immunity-without-liver-inflammation
#10
JOURNAL ARTICLE
Chunxiao Xu, Xueyuan Zhou, Lindsay Webb, Sireesha Yalavarthi, Wenxin Zheng, Somdutta Saha, Rene Schweickhardt, Maria Soloviev, Molly H Jenkins, Susanne Brandstetter, Natalya Belousova, Marat Alimzhanov, Brian Rabinovich, Amit M Deshpande, Neil Brewis, Laura Helming
The costimulatory receptor CD137 (also known as TNFRSF9 or 4-1BB) sustains effective cytotoxic T-cell responses. Agonistic anti-CD137 cancer immunotherapies are being investigated in clinical trials. Development of the first-generation CD137-agonist monotherapies utomilumab and urelumab was unsuccessful due to low antitumor efficacy mediated by the epitope recognized on CD137 or hepatotoxicity mediated by FcγR ligand-dependent CD137 activation, respectively. M9657 was engineered as a tetravalent bispecific antibody (mAb2 TM) in a human IgG1 backbone with LALA mutations to reduce binding to Fcγ receptors...
December 13, 2023: Cancer Immunology Research
https://read.qxmd.com/read/38067238/validation-of-a-gene-expression-approach-for-the-cytological-diagnosis-of-epithelioid-and-biphasic-pleural-mesothelioma-on-a-consecutive-series
#11
JOURNAL ARTICLE
Rossella Bruno, Anello Marcello Poma, Greta Alì, Agnese Proietti, Alessandro Ribechini, Antonio Chella, Gabriella Fontanini
Cytological diagnosis of pleural mesothelioma (PM) is controversial, even using ancillary markers (BAP1, MTAP and CDKN2A). Here, we aimed to prospectively validate a previously developed 117-gene expression panel for the differential cytological diagnosis of epithelioid, biphasic PM and mesothelial hyperplasia. Seventy-seven pleural effusions were classified using the 117-gene expression levels (NanoString system). Sixty-eight cases were also screened for ancillary markers. The performance of both gene panel and ancillary markers was evaluated using ROC metrics...
November 22, 2023: Cancers
https://read.qxmd.com/read/38027361/assessment-of-novel-mesothelin-specific-human-antibody-domain-vh-fc-fusion-proteins-based-pet-agents
#12
JOURNAL ARTICLE
Zehua Sun, Ambika P Jaswal, Xiaojie Chu, Harikrishnan Rajkumar, Angel G Cortez, Robert Edinger, Max Rose, Anders Josefsson, Abhinav Bhise, Ziyu Huang, Rieko Ishima, John W Mellors, Dimiter S Dimitrov, Wei Li, Jessie R Nedrow
Mesothelin (MSLN) is a tumor-associated antigen found in a variety of cancers and is a target for imaging and therapeutic applications in MSLN-expressing tumors. We have developed high affinity anti-MSLN human VH domain antibodies, providing alternative targeting vectors to conventional IgG antibodies that are associated with long-circulating half-lives and poor penetration of tumors, limiting antitumor activity in clinical trials. Based on two newly identified anti-MSLN VH binders (3C9, 2A10), we generated VH-Fc fusion proteins and modified them for zirconium-89 radiolabeling to create anti-MSLN VH-Fc PET tracers...
November 21, 2023: ACS Omega
https://read.qxmd.com/read/38007403/ferroptosis-related-genes-prognostic-signature-for-pancreatic-cancer-and-immune-infiltration-potential-biomarkers-for-predicting-overall-survival
#13
JOURNAL ARTICLE
Lei Wang, Zixuan Wu, Chen Xu, Hang Ye
BACKGROUND: Pancreatic adenocarcinoma (PAAD) constitutes a lethal malignancy, notorious for its elevated mortality rates due to the difficulties in early diagnosis and rapid metastasis. The emerging paradigm of ferroptosis-an iron-catalyzed, regulated cell death distinguished by the accrual of lipid peroxides-has recently garnered scholarly focus. However, the expression landscape of ferroptosis-related genes (FRGs) in PAAD and their prognostic implications remain enigmatic. METHODS: We undertook a rigorous quantification of FRGs in PAAD samples, sourcing data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases...
November 25, 2023: Journal of Cancer Research and Clinical Oncology
https://read.qxmd.com/read/37998743/advances-in-car-t-cell-therapy-for-non-small-cell-lung-cancer
#14
REVIEW
Hong Yun Ma, Jeeban Das, Conor Prendergast, Dorine De Jong, Brian Braumuller, Jacienta Paily, Sophia Huang, Connie Liou, Anna Giarratana, Mahdie Hosseini, Randy Yeh, Kathleen M Capaccione
Since its first approval by the FDA in 2017, tremendous progress has been made in chimeric antigen receptor (CAR) T cell therapy, the adoptive transfer of engineered, CAR-expressing T lymphocyte. CAR T cells are all composed of three main elements: an extracellular antigen-binding domain, an intracellular signaling domain responsible for T cell activation, and a hinge that joins these two domains. Continuous improvement has been made in CARs, now in their fifth generation, particularly in the intracellular signaling domain responsible for T cell activation...
November 12, 2023: Current Issues in Molecular Biology
https://read.qxmd.com/read/37914528/mesothelin-expression-in-gynecologic-carcinosarcoma-clinicopathological-significance-and-correlation-with-her2-expression
#15
JOURNAL ARTICLE
Rui Kitadai, Tadaaki Nishikawa, Hiroshi Yoshida, Chiharu Mizoguchi, Kasumi Yamamoto, Tomoyasu Kato, Kan Yonemori
OBJECTIVE: This study aimed to evaluate mesothelin (MSLN) expression and determine its clinical significance and correlation with human epidermal growth factor receptor 2 (HER2) expression in gynecological carcinosarcoma. METHODS: We retrospectively evaluated patients with uterine carcinosarcoma (UCS) and ovarian carcinosarcoma (OCS) who underwent surgery between 1997 and 2019. Immunohistochemical staining of formalin-fixed, paraffin-embedded specimens for MSLN (clone SP74) and HER2 (clone 4A5) was also performed...
October 12, 2023: Journal of Gynecologic Oncology
https://read.qxmd.com/read/37894284/exploring-the-tumor-suppressing-potential-of-psca-in-pancreatic-ductal-adenocarcinoma
#16
JOURNAL ARTICLE
Kexin Li, Qingji Huo, Kazumasa Minami, Keisuke Tamari, Kazuhiko Ogawa, Sungsoo Na, Melissa L Fishel, Bai-Yan Li, Hiroki Yokota
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with low survival rates. We explored an innovative therapeutic approach by leveraging prognostic oncogenic markers. Instead of inhibiting these marker genes, we harnessed their tumor-modifying potential in the extracellular domain. Surprisingly, many of the proteins highly expressed in PDAC, which is linked to poor survival, exhibited tumor-suppressing qualities in the extracellular environment. For instance, prostate stem cell antigens (PSCA), associated with reduced survival, acted as tumor suppressors when introduced extracellularly...
October 10, 2023: Cancers
https://read.qxmd.com/read/37869242/biology-of-mesothelin-and-clinical-implications-a-review-of-existing-literature
#17
REVIEW
Brendan L Hagerty, Kazuaki Takabe
Since its discovery in 1992, mesothelin (MSLN) has generated significant interest as a therapeutic target. A number of characteristics make it ideal for this purpose. First, it is not expressed on the parenchyma of any vital organs. Second, it is differentially expressed on a number of cancer types that have relatively poor prognosis and lack effective systemic options. Third, it is expressed on the cell membrane making it accessible to large molecule targeted therapies. However, unlike other drug targets that have been exploited for therapeutic benefit, the precise function of MSLN, why it is expressed in certain cancers, and its biological role have not been clearly elucidated...
October 2023: World Journal of Oncology
https://read.qxmd.com/read/37848682/functional-enhancement-of-mesothelin-targeted-truc-t-cells-by-a-pd1-cd28-chimeric-switch-receptor
#18
JOURNAL ARTICLE
Derrick McCarthy, Michael Lofgren, Amy Watt, Holly Horton, Philippe Kieffer-Kwon, Jian Ding, Sebastian Kobold, Patrick A Baeuerle, Robert Hofmeister, Dario A Gutierrez, Robert Tighe
T cells expressing a mesothelin (MSLN)-specific T cell receptor fusion construct (TRuC® ), called TC-210, have demonstrated robust antitumor activity in preclinical models of mesothelioma, ovarian cancer, and lung cancer. However, they are susceptible to suppression by the programmed cell death protein 1 (PD-1)/programmed cell death protein ligand 1 (PD-L1) axis and lack intrinsic costimulatory signaling elements. To enhance the function of anti-MSLN TRuC-T cells, chimeric switch receptors (CSRs) have been designed to co-opt the immunosuppressive PD-1/PD-L1 axis and to deliver a CD28-mediated costimulatory signal...
October 18, 2023: Cancer Immunology, Immunotherapy: CII
https://read.qxmd.com/read/37783583/corrigendum-to-neat1-culprit-lncrna-linking-pigc-msln-and-cd80-in-triple-negative-breast-cancer-life-sci-volume-299-2022-120523
#19
Nada H Hussein, Monica Armanious, Reda A Eissa, M de Bruyn, Hend M El Tayebi
No abstract text is available yet for this article.
September 30, 2023: Life Sciences
https://read.qxmd.com/read/37775021/novel-mesothelin-targeted-chimeric-antigen-receptor-modified-unkt-cells-are-highly-effective-in-inhibiting-tumor-progression
#20
JOURNAL ARTICLE
Wei Jiang, Guosheng Gu, Yumin Zhang, Yushuai Song, Ming Shi, Gang Wang, Huizhong Li, Tingting Tao, Jianhua Qin, Xianliang Li, Hongtao Jia, Feng Jiao, Weidong Xu, Xiaoyi Huang
The design of chimeric antigen receptors (CAR) significantly enhances the antitumor efficacy of T cells. Although some CAR-T products have been approved by FDA in treating hematological tumors, adoptive immune therapy still faces many difficulties and challenges in the treatment of solid tumors. In this study, we reported a new strategy to treat solid tumors using a natural killer-like T (NKT) cell line which showed strong cytotoxicity to lyse 15 cancer cell lines, safe to normal cells and had low or no Graft-versus-host activity...
September 27, 2023: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
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