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The safety, tolerability, pharmacokinetics and pharmacodynamics of an optimized dual GLP-1/GIP receptor agonist (BGM0504) in healthy volunteers: A dose-escalation Phase I study.
Diabetes Obes Metab
January 2025
Research Center of Clinical Pharmacology, The First Affiliated Hospital of Yunnan University of Chinese Medicine, Kunming, China.
Objective: Previous experiments have demonstrated that BGM0504, a GLP-1R/GIPR dual agonist drug by molecular dynamics-guided optimization, had enhanced agonistic activity compared to tirzepatide. This study aims to investigate its safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) in Chinese healthy volunteers.
Methods: A randomized, double-blind, placebo-controlled and dose-escalation Phase I study was conducted as follows: a single dose (2.
VACCIMEL, an allogeneic melanoma vaccine, efficiently triggers T cell immune responses against neoantigens and alloantigens, as well as against tumor-associated antigens.
Front Immunol
January 2025
Centro de Investigaciones Oncológicas (FUCA), Fundación Cáncer, Ciudad Autónoma de Buenos Aires, Argentina.
VACCIMEL is a therapeutic cancer vaccine composed of four irradiated allogeneic human melanoma cell lines rationally selected to cover a wide range of melanoma tumor-associated antigens (TAA). We previously demonstrated that vaccination in the adjuvant setting prolonged the distant-metastasis-free survival of cutaneous melanoma patients and that T cells reactive to TAA and the patient's private neoantigens increased during treatment. However, immune responses directed to vaccine antigens that may arise from VACCIMEL's somatic mutations and human polymorphisms remain unexplored.
View Article and Find Full Text PDFCase report: A novel germline loss-of-function mutation in the STAT1 transactivation domain in two Chinese siblings, with the elder sibling presenting with multifocal Calmette-Guerin osteomyelitis.
Front Immunol
January 2025
Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, Hong Kong, Hong Kong SAR, China.
Signal transducer and activator of transcription 1 (STAT1) gene mutations have broad clinical phenotypes, classified by the inheritance pattern and functional state. Individuals with autosomal dominant STAT1 deficiency are more susceptible to intracellular bacteria, the hallmark of which is Mendelian susceptibility to mycobacterial diseases (MSMDs) that are associated with increased risks of invasive disease by weakly virulent mycobacteria. We report a novel heterozygous missense mutation in exon 23 of the STAT1 gene (NM_007315.
View Article and Find Full Text PDFMagnitude and dynamics of the T-cell response to SARS-CoV-2 infection at both individual and population levels.
Front Immunol
January 2025
Adaptive Biotechnologies, Seattle, WA, United States.
Introduction: T cells are involved in the early identification and clearance of viral infections and also support the development of antibodies by B cells. This central role for T cells makes them a desirable target for assessing the immune response to SARS-CoV-2 infection.
Methods: Here, we combined two high-throughput immune profiling methods to create a quantitative picture of the T-cell response to SARS-CoV-2.
An allelic atlas of immunoglobulin heavy chain variable regions reveals antibody binding epitope preference resilient to SARS-CoV-2 mutation escape.
Front Immunol
January 2025
State Key Laboratory of Respiratory Disease, Guangdong Laboratory of Computational Biomedicine, Center for Cell Lineage Research, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
Background: Although immunoglobulin (Ig) alleles play a pivotal role in the antibody response to pathogens, research to understand their role in the humoral immune response is still limited.
Methods: We retrieved the germline sequences for the IGHV from the IMGT database to illustrate the amino acid polymorphism present within germline sequences of IGHV genes. We aassembled the sequences of IgM and IgD repertoire from 130 people to investigate the genetic variations in the population.
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