A5026041577- Monoclonal and Polyclonal Antibodies Research
- Protein purification and stability
- HER2/EGFR in Cancer Research
- Influenza Virus Research Studies
- Glycosylation and Glycoproteins Research
- Lymphoma Diagnosis and Treatment
- Biosimilars and Bioanalytical Methods
- Respiratory viral infections research
- CAR-T cell therapy research
- Cytomegalovirus and herpesvirus research
- Antimicrobial Resistance in Staphylococcus
- Platelet Disorders and Treatments
- Chronic Lymphocytic Leukemia Research
- Receptor Mechanisms and Signaling
- Liver Disease Diagnosis and Treatment
- Nutrition and Health in Aging
- Advanced Biosensing Techniques and Applications
- T-cell and B-cell Immunology
- Radiopharmaceutical Chemistry and Applications
- Immunotherapy and Immune Responses
- Liver Disease and Transplantation
- Herpesvirus Infections and Treatments
- COVID-19 and Mental Health
- Cancer Immunotherapy and Biomarkers
- Renal Transplantation Outcomes and Treatments
Sichuan University
2016-2025
West China Hospital of Sichuan University
2016-2025
Sixth Affiliated Hospital of Sun Yat-sen University
2025
Sun Yat-sen University
2012-2025
Sun Yat-sen University Cancer Center
2025
First People’s Hospital of Zunyi
2024
IGM Biosciences (United States)
2023
Q Chem (United States)
2023
Guizhou Provincial People's Hospital
2021-2022
Gilead Sciences (United States)
2022
The pharmacokinetics (PK) of therapeutic antibodies is determined by target and non-target mediated mechanisms. These antibody-specific factors need to be considered during prediction human PK based upon preclinical information. Principles allometric scaling established for small molecules using data from multiple animal species cannot directly applied antibodies. Here, different methods projecting clearance (CL) 13 monoclonal (mAbs) exhibiting linear over the tested dose ranges were...
A majority of human therapeutic antibody candidates show pharmacokinetic properties suitable for clinical use, but an unexpectedly fast clearance is sometimes observed that may limit the utility. Pharmacokinetic data in cynomolgus monkeys collected a panel 52 antibodies showed broad distribution target-independent values (2.4–61.3 mL/day/kg), with 15 (29%) having > 10 mL/day/kg. Alteration interaction recycling FcRn receptor did not account faster than expected antibodies; off-target binding...
MPDL3280A is a human monoclonal antibody that targets programmed cell death-1 ligand 1 (PD-L1), and exerts anti-tumor activity mainly by blocking PD-L1 interaction with (PD-1) B7.1. It being investigated as potential therapy for locally advanced or metastatic malignancies. The purpose of the study reported here was to characterize pharmacokinetics, pharmacodynamics, tissue distribution tumor penetration and/or chimeric anti-PD-L1 PRO304397 help further clinical development. pharmacokinetics...
Pharmacokinetic (PK) testing of a humanized (κI, VH3 framework) and affinity matured anti-hepatitis C virus E2-glycoprotein (HCV-E2) antibody (hu5B3.κ1VH3.v3) in rats revealed unexpected fast clearance (34.9 mL/day/kg). This binds to the rat recycling receptor FcRn as expected for human IgG1 does not display non-specific binding baculovirus particles an assay that is correlated with cynomolgus monkey. The antigen expressed so target-dependent contribute PK. Removal maturation changes...
ABSTRACT Cytomegalovirus (CMV) infection is a significant complication after kidney transplantation. We examined the ability of RG7667, combination two monoclonal antibodies, to prevent CMV in high-risk transplant recipients randomized, double-blind, placebo-controlled trial. CMV-seronegative from CMV-seropositive donor (D+R−) were randomized receive RG7667 ( n = 60) or placebo at time and 1, 4, 8 weeks posttransplant. Patients monitored for viremia every 1 2 posttransplant 24 weeks. who had...
Staphylococcus aureus causes serious bacterial infections with high morbidity and mortality, necessitating the discovery of new antibiotics. DSTA4637S is a novel antibody-antibiotic conjugate designed to target intracellular S. that not adequately eliminated by current standard-of-care
The neonatal Fc receptor (FcRn) plays a critical role in maintaining homeostasis of IgG antibodies. Recent studies have shown that the FcRn-IgG interaction can be modulated to alter pharmacokinetics antibody. This has been achieved by altering amino acid residues FcRn-binding domain antibody, resulting change pH-dependent binding affinity antibody FcRn. purpose this study was examine impact FcRn on with changes Asn434 residue. Two anti-tumor necrosis factor-α monoclonal (mAb) variants (N434A...
Antibody-drug conjugates (ADC), potent cytotoxic drugs linked to antibodies via chemical linkers, allow specific targeting of neoplastic cells. We have used this technology develop the ADC DCDT2980S that targets CD22, an antigen with expression limited B cells and vast majority non-Hodgkin lymphomas (NHL). consists a humanized anti-CD22 monoclonal IgG1 antibody microtubule-disrupting agent, monomethyl auristatin E (MMAE), reduced cysteines protease cleavable linker,...
MHAA4549A, a human monoclonal antibody targeting the hemagglutinin stalk region of influenza A virus (IAV), is being developed as therapeutic for patients hospitalized with severe IAV infection. The safety and efficacy MHAA4549A were assessed in randomized, double-blind, placebo-controlled, dose-ranging study challenge model. One hundred healthy volunteers inoculated A/Wisconsin/67/2005 (H3N2) and, 24 to 36 h later, administered single intravenous dose either placebo, (400, 1,200, or 3,600...
Therapeutic options currently available for metastatic castration-resistant prostate cancer (mCRPC) do not extend median overall survival >6 months. Therefore, the development of novel and effective therapies mCRPC represents an urgent medical need. T cell engagers (TCEs) have emerged as a promising approach treatment due to their targeted mechanism action. However, challenges remain in clinic limited efficacy TCEs observed thus far solid tumors well toxicities associated with cytokine...
Abstract Mosunetuzumab (Mosun) is a CD20xCD3 T‐cell engaging bispecific antibody that redirects T cells to eliminate malignant B cells. The approved step‐up dose regimen of 1/2/60/30 mg IV designed mitigate cytokine release syndrome (CRS) and maximize efficacy in early cycles. A population pharmacokinetic (popPK) model was developed from 439 patients with relapsed/refractory B‐Cell Non‐Hodgkin lymphoma receiving Mosun monotherapy, including fixed dosing (0.05–2.8 every 3 weeks (q3w)) Cycle 1...
The neonatal Fc receptor (FcRn) plays an important and well-known role in immunoglobulin G (IgG) catabolism; however, its the disposition of IgG after subcutaneous (SC) administration, including bioavailability, is relatively unknown. To examine potential effect FcRn on SC we engineered three anti-amyloid β monoclonal antibody (mAb) reverse chimeric mouse IgG2a (mIgG2a) variants (I253A.H435A, N434H N434Y) with different binding affinities to (mFcRn) compared their bioavailability that...
The incidence of cryptococcal meningitis (CM) and tuberculous (TBM) have gradually increased in recent years. These two types are easily misdiagnosed which leads to a poor prognosis. In this study we compared differences clinical features prognostic factors non-HIV adults with CM TBM.We retrospectively reviewed the medical records TBM patients from January 2008 December 2015 our university hospital China. data included demographic characteristics, laboratory results, imaging findings,...
MHAA4549A is a human immunoglobulin G1 (IgG1) monoclonal antibody that binds to highly conserved epitope on the stalk of influenza A hemagglutinin and blocks hemagglutinin-mediated membrane fusion in endosome, neutralizing all known strains. Pharmacokinetics (PK) its related antibodies were determined DBA/2J Balb-c mice at 5 mg/kg cynomolgus monkeys 100 as single intravenous dose. Serum samples analyzed for concentrations using an ELISA PK was evaluated WinNonlin software. Human profiles...
A cell-based assay employing Madin–Darby canine kidney cells stably expressing human neonatal Fc receptor (FcRn) heavy chain and β2-microglobulin genes was developed to measure transcytosis of monoclonal antibodies (mAbs) under conditions relevant the FcRn-mediated immunoglobulin G (IgG) salvage pathway. The FcRn-dependent is modeled reflect combined effects nonspecific interactions between mAbs cells, cellular uptake via pinocytosis, pH-dependent with FcRn, dynamics intracellular...
Human cytomegalovirus (HCMV) is the most common cause of congenital virus infection. Congenital HCMV infection occurs in 0.2–1% all births, and causes birth defects developmental abnormalities, including sensorineural hearing loss delay. Several key studies have established guinea pig as a tractable model for study shown that polyclonal antibodies can be protective [1]–[3]. In this study, we demonstrate an anti-guinea CMV (GPCMV) glycoprotein H/glycoprotein L neutralizing monoclonal antibody...
Hospitalized patients with severe influenza are at significant risk for morbidity and mortality. MHAA4549A is a human monoclonal immunoglobulin (Ig) G1 antibody that binds to highly conserved stalk region of the A virus hemagglutinin protein neutralizes all tested seasonal strains. Two phase 1 trials examined safety, tolerability, pharmacokinetics in healthy volunteers. Both single ascending-dose were randomized, double blinded, placebo controlled. Trial randomized 21 adults into four...
Polatuzumab vedotin is a CD79b-directed antibody-drug conjugate that targets B cells and delivers the cytotoxic payload monomethyl auristatin E (MMAE). The phase III POLARIX study (NCT03274492) evaluated polatuzumab in combination with rituximab, cyclophosphamide, doxorubicin, prednisone (R-CHP) as first-line treatment of diffuse large B-cell lymphoma (DLBCL). To examine dosing decisions for this regimen, population pharmacokinetic (popPK) analysis, using previously developed popPK model,...
ABSTRACT Cytomegalovirus can cause debilitating and life-threatening disease in newborns infected utero immunocompromised individuals, including transplant recipients. RG7667 is a unique combination of two monoclonal antibodies that binds glycoprotein complexes on the surface cytomegalovirus inhibits its entry into host cells. A phase 1 first-in-human, randomized, double-blind, placebo-controlled, dose-escalation study given intravenously was conducted 181 healthy adults. The involved single...