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Immunotherapy of Chronic Myeloid Leukemia
Published in Jorge Cortes, Michael Deininger, Chronic Myeloid Leukemia, 2006
Bocchia Monica, Lauria Francesco
Proteinase-3 (PR3) or myeloblastin is a 26-kd neutral serine protease normally expressed in hematopoietic tissues and highly expressed in myeloid haematological malignancies. PR1, an HLA-A2.1-restricted nonamer peptide derived from PR3, has been identified as a tumor-specific antigen in myeloid leukemia. Cytotoxic T lymphocytes recognizing PR1 that are capable of lysing fresh leukemia cells have been detected in CML patients and have been implicated in the clearance of malignant cells in patients treated with IFN-a or stem cell transplantation (SCT) (24). Vaccinations of PR1 peptide in Montanide were administered subcutaneously every three weeks for a total of three doses to 10 CML patients not responding to treatment or with relapsed disease (25). Preliminary reports indicate that a significant increase in PR1 CTLs was evident in about 60% of vaccinated patients. Clinical responses included one CCyR and stable disease with some hematologic improvement in three cases. Responses were correlated with the induction of PR1-specific CTLs with a central memory (CCR7+) phenotype, indicative of a self-renewing population (26). However, there is good evidence that imatinib therapy down-regulates PR3 expression in CML cells and this could potentially reduce the antitumor activity of this approach (27). In fact, especially in the context of MRD persisting on prolonged treatment with imatinib, leukemic cells may harbor only minimal amounts of PR3 that are insufficient for proper PR1 peptide HLA presentation. Consequently, PR1-specific CTLs induced with the vaccinations may be unable to recognize and clear residual cells due to an inadequate number of PR-1–HLA complexes on the cell surface. One way to circumvent this problem could be to stop imatinib treatment temporarily after immunization with PR-1 vaccine in order to “restore” the PR3 content of the residual CML cells and allow their recognition and elimination by PR-1 specific CTLs.
The diagnostic role and clinical association of serum proteinase 3 anti-neutrophil cytoplasmic antibodies in Chinese patients with inflammatory bowel disease
Published in Scandinavian Journal of Gastroenterology, 2020
Yan Xu, Fei Xu, Wenjie Li, Mengting Li, Shouquan Dong, Yupeng Zhang, Gary L. Norman, Qiu Zhao, Lan Liu
Proteinase 3 (PR3), a serine proteinase, also called myeloblastin [6], belongs to the family of neutrophil microbicidal serine proteinases that are stored within azurophilic granules [7]. They are considered proinflammatory proteinases because they mediate deleterious effects on host tissues during inflammation [8,9]. When expressed in the outer lobule of the neutrophil plasma membrane, they are considered a risk factor for vasculitis and rheumatoid arthritis and are the preferred target for anti-neutrophil cytoplasmic autoantibody (ANCA) in granulomatosis with polyangiitis (GPA), also known as Wegener’s granulomatosis (WG). PR3-ANCA is a biomarker antibody for ANCA-associated vasculitis, especially for GPA. Some studies have described PR3-ANCA positive patients with overlapping IBD and GPA characteristics [10–12].
Low P4HA2 and high PRTN3 expression predicts poor survival in patients with pancreatic cancer
Published in Scandinavian Journal of Gastroenterology, 2019
Dingyuan Hu, Daniel Ansari, Qimin Zhou, Agata Sasor, Katarzyna Said Hilmersson, Roland Andersson
PRTN3, also known as myeloblastin or c-ANCA (cytoplasmic pattern of antineutrophil cytoplasmic autoantibodies) antigen, is a serine protease secreted by cells of myeloid lineage [13] and allocated to the cell surface of neutrophils [14] and endothelial cells [15]. PRTN3 is related to inflammatory processes, but its link to neoplasia is less understood. Sharing structural similarity with elastase, PRTN3 has an elastase-like specificity for small aliphatic residues (Ala, Val, Ser, Met) and degrades a variety of matrix proteins in vitro including fibronectin, laminin, vitronectin, and collagen [16]. PRTN3 is also thought to be involved in MMP activation, hence potentially being involved in tumor invasion and metastasis [17,18]. Moreover, it has been found that PRTN3 induces phosphorylation and nuclear translocation of p44/p42 and JNK1, leading to cancer cell motility, through a nonproteolytic way [19]. Notably, recent studies revealed that PRTN3 expressed by neutrophils within the TME can be taken up by breast cancer and melanoma cells, which in turn increase the susceptibility to PR1-targeting therapies [14,20].
Validation of a proteomic biomarker panel to diagnose minor-stroke and transient ischaemic attack: phase 2 of SpecTRA, a large scale translational study
Published in Biomarkers, 2018
Andrew M. Penn, Maximilian B. Bibok, Viera K. Saly, Shelagh B. Coutts, Mary L. Lesperance, Robert F. Balshaw, Kristine Votova, Nicole S. Croteau, Anurag Trivedi, Angela M. Jackson, Janka Hegedus, Evgenia Klourfeld, Amy Y. X. Yu, Charlotte Zerna, Jayesh Modi, Philip A. Barber, Gordon Hoag, Christoph H. Borchers
The plasma-proteins comprising our 16-protein biomarker panel were: (1) adiponectin (ADPN); (2) apolipoprotein B-100 (ApoB100); (3) coagulation factor IX (F9); (4) coagulation factor V (F5); (5) coagulation factor X (FX); (6) hyaluronan-binding protein 2 (HABP2); (7) heparin cofactor 2 (HCII); (8) hemopexin (HPX); (9) insulin-like growth factor-binding protein 3 (IGFBP-3); (10) L-selectin (LSEL); (11) myeloblastin (MBN); (12) plasma serine protease inhibitor (PCI); (13) serum paraoxonase/lactonase 3 (PON3); (14) thrombospondin-1 (TSP-1); (15) vascular endothelial growth factor D (VEGF-D) and (16) von Willebrand factor (vWF).