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A humanized anti-MSLN×4-1BB bispecific antibody exhibits potent antitumour activity through 4-1BB signaling activation and fc function without systemic toxicity.
J Transl Med
January 2025
Department of Medical Oncology, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Anhui Provincial Cancer Hospital, Hefei, 230031, Anhui, China.
Background: Agonistic monoclonal antibodies targeting 4-1BB/CD137 have shown preclinical promise, but their clinical development has been limited by severe liver toxicity or limited efficacy. Therefore, a safe and efficient immunostimulatory molecule is urgently needed for cancer immunotherapy.
Methods: A novel anti-MSLN×4-1BB bispecific antibody (bsAb) was generated via antibody engineering, and its affinity and activity were detected via enzyme-linked immunosorbent assay (ELISA), flow cytometry, and T-cell activation and luciferase reporter assays.
Excess shed mesothelin disrupts pancreatic cancer cell clustering to impair peritoneal colonization.
FASEB J
December 2024
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Peritoneum is the second most common site of metastasis in patients with pancreatic ductal adenocarcinoma (PDAC). Peritoneal colonization is impaired in PDAC cells with knockout (KO) of the cancer surface antigen mesothelin (MSLN) or by introducing Y318A mutation in MSLN to prevent binding to mucin-16 (MUC-16). MSLN has a membrane-bound form but is also shed to release soluble MSLN (sMSLN).
View Article and Find Full Text PDFDevelopment of a CD39 nanobody and its enhancement to chimeric antigen receptor T cells efficacy against ovarian cancer in preclinical studies.
Theranostics
October 2024
Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 200092, China.
: CD39, a key ectonucleotidase that drives adenosine production, acts as a critical immunosuppressive checkpoint in cancer. Although it has shown promise as a therapeutic target, clinical trials are demonstrating the need for more potent targeting approaches. This need is driving innovation towards the development of novel antibodies and the exploration of strategic combinations with a range of immunotherapies.
View Article and Find Full Text PDFSoluble mesothelin-related peptide as a prognosticator in pleural mesothelioma patients receiving checkpoint immunotherapy.
J Thorac Cardiovasc Surg
October 2024
Systems Onco-Immunology Laboratory, David J. Sugarbaker Division of Thoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Tex; Division of Hemato-Oncology, Department of Medicine, Baylor College of Medicine, Houston, Tex; David J. Sugarbaker Division of Thoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Tex. Electronic address:
Article Synopsis
- Immune checkpoint therapy (ICT) has changed the treatment landscape for malignant pleural mesothelioma (MPM), but nearly half of patients do not see benefits, emphasizing the need for predictive biomarkers.
- This study evaluated the prognostic value of serum soluble mesothelin-related peptide (SMRP) and PD-L1 levels in 125 MPM patients undergoing ICT, using statistical analyses to determine their impact on overall survival (OS).
- Results showed that higher pre-ICT SMRP levels are linked to poorer prognosis, with low levels indicating better survival outcomes, suggesting that SMRP could serve as a valuable biomarker for future MPM treatment studies.
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