scholarly journals Development of a strategy and computational application to select candidate protein analogues with reduced HLA binding and immunogenicity

Immunology ◽  
2017 ◽  
Vol 153 (1) ◽  
pp. 118-132 ◽  
Author(s):  
Sandeep Kumar Dhanda ◽  
Alba Grifoni ◽  
John Pham ◽  
Kerrie Vaughan ◽  
John Sidney ◽  
...  
2019 ◽  
Vol 19 (1) ◽  
pp. 7-19 ◽  
Author(s):  
Xiao-Xiao Lu ◽  
Shao-Zhen Zhao

Background: As one of the main blinding ocular diseases, corneal blindness resulted from neovascularization that disrupts the angiogenic privilege of corneal avascularity. Following neovascularization, inflammatory cells are infiltrating into cornea to strengthen corneal injury. How to maintain corneal angiogenic privilege to treat corneal disease has been investigated for decades. Methodology: Local administration of viral and non-viral-mediated anti-angiogenic factors reduces angiogenic protein expression in situ with limited or free of off-target effects upon gene delivery. Recently, Mesenchymal Stem Cells (MSCs) have been studied to treat corneal diseases. Once MSCs are manipulated to express certain genes of interest, they could achieve superior therapeutic efficacy after transplantation. Discussion: In the text, we first introduce the pathological development of corneal disease in the aspects of neovascularization and inflammation. We summarize how MSCs become an ideal candidate in cell therapy for treating injured cornea, focusing on cell biology, property and features. We provide an updated review of gene-based therapies in animals and preclinical studies in the aspects of controlling target gene expression, safety and efficacy. Gene transfer vectors are potent to induce candidate protein expression. Delivered by vectors, MSCs are equipped with certain characters by expressing a protein of interest, which facilitates better for MSC-mediated therapeutic intervention for the treatment of corneal disease. Conclusion: As the core of this review, we discuss how MSCs could be engineered to be vector system to achieve enhanced therapeutic efficiency after injection.


2021 ◽  
pp. 136113
Author(s):  
Yukari Nagakura ◽  
Ryoji Ide ◽  
Chikako Saiki ◽  
Nana Sato Hashizume ◽  
Toshio Imai

2000 ◽  
Vol 275 (13) ◽  
pp. 9890-9891
Author(s):  
Xibao Liu ◽  
Weiching Wang ◽  
Brij B. Singh ◽  
Timothy Lockwich ◽  
Julie Jadlowiec ◽  
...  

2021 ◽  
pp. 1-13
Author(s):  
Teva Phanaksri ◽  
Yodying Yingchutrakul ◽  
Sittiruk Roytrakul ◽  
Sattrachai Prasopdee ◽  
Anthicha Kunjantarachot ◽  
...  

BACKGROUND: Patients infected with a parasite often develop opisthorchiasis viverrini, which often progresses into cholangiocarcinoma (CCA) due to the asymptomatic nature of the infection. Currently, there are no effective diagnostic methods for opisthorchiasis or cholangiocarcinoma. OBJECTIVE: The aim of this study was to identify the host-responsive protein that can be developed as a diagnostic biomarker of opisthorchiasis and cholangiocarcinoma. METHODS: Plasma samples were collected from non-OVCCA, OV, and CCA subjects, and the proteomes were investigated by LC-MS/MS. Venn diagrams and protein network prediction by STITCH were used to identify the potential biomarkers. The level of candidate protein, the plasma checkpoint protein 1 (Chk1), was measured by indirect enzyme-linked immunosorbent assay (ELISA). RESULTS: Chk1 was present in the center of the protein network analysis in both the OV and CCA groups. In addition, the plasma Chk1 levels were significantly increased in both groups (P< 0.05). The sensitivity of the opisthorchiasis viverrini and cholangiocarcinoma was 59.38% and 65.62%, respectively, while the specificity of both was 85.71%. CONCLUSION: Chk1 was identified by differential plasma proteomes and was increased in O. viverrini-infected and cholangiocarcinoma-derived plasma samples. Higher levels of plasma Chk1 levels may serve as a potential diagnostic biomarker for opisthorchiasis and cholangiocarcinoma.


2012 ◽  
Vol 77 ◽  
pp. 40-58 ◽  
Author(s):  
Megan A.S. Penno ◽  
Manuela Klingler-Hoffmann ◽  
Julie A. Brazzatti ◽  
Alex Boussioutas ◽  
Tracy Putoczki ◽  
...  

Blood ◽  
2003 ◽  
Vol 101 (12) ◽  
pp. 4930-4936 ◽  
Author(s):  
Lotta Hansson ◽  
Hodjattallah Rabbani ◽  
Jan Fagerberg ◽  
Anders Österborg ◽  
Håkan Mellstedt

Abstract The idiotypic structure of the monoclonal immunoglobulin (Ig) in multiple myeloma (MM) might be regarded as a tumor-specific antigen. The present study was designed to identify T-cell epitopes of the variable region of the Ig heavy chain (VH) in MM (n = 5) using bioinformatics and analyze the presence of naturally occurring T cells against idiotype-derived peptides. A large number of human-leukocyte-antigen (HLA)–binding (class I and II) peptides were identified. The frequency of predicted epitopes depended on the database used: 245 in bioinformatics and molecular analysis section (BIMAS) and 601 in SYFPEITHI. Most of the peptides displayed a binding half-life or score in the low or intermediate affinity range. The majority of the predicted peptides were complementarity-determining region (CDR)–rather than framework region (FR)–derived (52%-60% vs 40%-48%, respectively). Most of the predicted peptides were confined to the CDR2-FR3-CDR3 “geographic” region of the Ig-VH region (70%), and significantly fewer peptides were found within the flanking (FR1-CDR1-FR2 and FR4) regions (P &lt; .01). There were 8– to 10–amino acid (aa) long peptides corresponding to the CDRs and fitting to the actual HLA-A/B haplotypes that spontaneously recognized, albeit with a low magnitude, type I T cells (interferon γ), indicating an ongoing major histocompatibility complex (MHC) class I–restricted T-cell response. Most of those peptides had a low binding half-life (BIMAS) and a low/intermediate score (SYFPEITHI). Furthermore, 15- to 20-aa long CDR1-3–derived peptides also spontaneously recognized type I T cells, indicating the presence of MHC class II–restricted T cells as well. This study demonstrates that a large number of HLA-binding idiotypic peptides can be identified in patients with MM. Such peptides may spontaneously induce a type I MHC class I– as well as class II–restricted memory T-cell response.


Author(s):  
Huw Davies ◽  
Ian Tarpey ◽  
Simon Stacey ◽  
Julian Hickling ◽  
Jennifer Bartholomew ◽  
...  

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