Synthetic humanized antibody libraries are frequently generated by random incorporation of changes at multiple positions in the antibody hypervariable regions. Although these libraries have very large theoretical diversities (>10(20)), the practical diversity that can be achieved by transformation of Escherichia coli is limited to about 10(10). To constrain the practical diversity to sequences that more closely mimic the diversity of natural human antibodies, we generated a scFv phage library using entirely pre-defined complementarity determining regions (CDR). We have used this library to select for novel antibodies against four human protein targets and demonstrate that identification of enriched sequences at each of the six CDRs in early selection rounds can be used to reconstruct a consensus antibody with selectivity for the target.
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http://dx.doi.org/10.1016/j.nbt.2015.11.005 | DOI Listing |
ACS Cent Sci
December 2024
Department of Chemistry, North Carolina State University, 2620 Yarbrough Dr., Raleigh, North Carolina 27695, United States.
Aptamers are oligonucleotide-based affinity reagents that are increasingly being used in various applications. Systematic evolution of ligands by exponential enrichment (SELEX) has been widely used to isolate aptamers for small-molecule targets, but it remains challenging to generate aptamers with high affinity and specificity for targets with few functional groups. To address this challenge, we have systematically evaluated strategies for optimizing the isolation of aptamers for (+)-methamphetamine, a target for which previously reported aptamers have weak or no binding affinity.
View Article and Find Full Text PDFPediatr Rheumatol Online J
December 2024
Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Objective: This systematic search and review aimed to evaluate the available literature on discontinuation of adalimumab and other tumor necrosis factor inhibitors (TNFi) for patients with well-controlled chronic inflammatory arthritides.
Methods: We conducted a publication search on adalimumab discontinuation from 2000-2023 using PubMed, CINAHL, EMBASE, and Cochrane Library. Included studies evaluated adalimumab discontinuation approaches, tapering schemes, and outcomes including successful discontinuation and recapture after flare, in patients with well-controlled disease.
PLoS One
December 2024
Department of Obstetrics and Gynaecology, West China Second University Hospital, Sichuan University, Chengdu, China.
Background: Mirvetuximab Soravtansine (MIRV) is a promising antibody‒drug conjugate (ADC) that targets folate receptor alpha (FRα), which is overexpressed in several types of solid tumors. In November 2022, MIRV was approved in the USA for the treatment of adult patients with FRα-positive, platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal cancer who received 1-3 prior systemic treatment regimens. Therefore, high-quality evidence for its efficacy and safety in different cancers is urgently needed.
View Article and Find Full Text PDFAntibodies (Basel)
December 2024
Department of Pharmacology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA.
Background/objectives: Anterior Gradient-2 (AGR2/PDIA17) is a member of the protein disulfide isomerase (PDI) family of oxidoreductases. AGR2 is up-regulated in several solid tumors, including pancreatic ductal adenocarcinoma (PDAC). Given the dire need for new therapeutic options for PDAC patients, we investigated the expression and function of AGR2 in PDAC and developed a novel series of affinity-matured AGR2-specific single-chain variable fragments (scFvs) and monoclonal antibodies.
View Article and Find Full Text PDFFront Immunol
December 2024
Institute of Transplantation Medicine, The Second Affiliated Hospital of Guangxi Medical University, Guangxi Clinical Research Center for Organ Transplantation, Guangxi Key Laboratory of Organ Donation and Transplantation, Nanning, Guangxi, China.
Objective: This study aims to assess the efficacy of pharmacological interventions in mitigating graft injury in transplant patients with antibody-mediated rejection (AMR) through a network meta-analysis (NMA).
Methods: A search was conducted on databases such as Cochrane Library, PubMed, EmBase, and Web of Science for randomized controlled trials (RCTs) on pharmacological interventions for alleviating graft injury following AMR. The search was performed for publications up to April 12, 2024.
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