scholarly journals Non-canonical Binding of an Antibody Resembling a Naïve B Cell Receptor Immunoglobulin to Hepatitis B Virus Capsids

2008 ◽  
Vol 379 (5) ◽  
pp. 1119-1129 ◽  
Author(s):  
Norman R. Watts ◽  
Giovanni Cardone ◽  
Joe G. Vethanayagam ◽  
Naiqian Cheng ◽  
Catharina Hultgren ◽  
...  
2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A297-A297
Author(s):  
Fu-Sheng Wang ◽  
Fanping Meng ◽  
Jiehua Jin ◽  
Yuanyuan Li ◽  
Regina Wanju Wong ◽  
...  

BackgroundWe have demonstrated the ability of Hepatitis-B-virus (HBV)-specific T cell receptor (TCR) bioengineered T cells to recognize and lyse Hepatocellular carcinoma (HCC) cells expressing HBV antigens derived from HBV-DNA integration in patients with liver transplant.1 LioCyx-M is an immunotherapeutic product composing of autologous T cells transiently modified with in-vitro transcribed mRNA encoding HBV-specific TCR. The transient TCR expression makes LioCyx -M amenable to a dose escalating posology.MethodsThe primary endpoint of this phase 1 trial is to assess the safety and tolerability of LioCyx-M in patients with advanced HBV-HCC without curative treatment options. Eligible patients were diagnosed with Barcelona clinic liver cancer stage B or C HCC (Child-Pugh < 7 points), receiving >1 year antiviral treatment prior to enrollment. These patients had matching HLA class I genotypes which present HBV encoded antigen. Peripheral blood was collected from each patient prior to each dose for LioCyx-M manufacturing. Patients received 4 escalating doses of 1×104 cells/kg, 1×105 cells/kg, 1×106 cells/kg, 5×106 cells/kg bodyweight (BW) in the first treatment cycle, each intravenously administered weekly. Patients underwent 1-month safety assessment post the 4th infusion, according to Common Terminology NCI CTCAE Version 4.0.3. If there were no dose associated toxicities, patients were eligible to continue administration of LioCyx-M at dose of 5 × 106 cells/kg BW weekly. Tumor response per RECIST 1.1 criteria and survival time were assessed.ResultsAt data cutoff (30 April 2020), eight patients were enrolled, with a median age of 53 (range: 49 - 67). These patients received a median number of 6 (range: 4 - 12) infusions of LioCyx-M. 1 patient developed Grade 3 elevations in alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST) and bilirubin after receiving LioCyx-M at dose level of 1×105 cells/kg BW. Another patient had Grade 1 transient fever after receiving LioCyx-M at dose level 5×106 cells/kg BW in the 4th, 5th and 6th infusions. No treatment-related adverse events (trAEs) such as cytokine release syndrome or neurotoxicity were observed. No fatal trAEs were observed. The median time to progression was 1.9 months (range: 0.2 - 9.5 months). The median overall survival was 34 months (range: 3 - 38.2 months).ConclusionsThe encouraging clinical outcome and tolerable safety highlight the good benefit-risk profile of LioCyx-M. Therefore, further exploration of efficacy of LioCyx-M treatment for advanced HBV-HCC is warranted in a Phase 2 proof-of-concept clinical study.AcknowledgementsFunding: Lion TCR.Trial RegistrationNCT03899415Ethics ApprovalThe study was approved by Fifth Medical Center of Chinese PLA General Hospital’s Ethics Board, approval number R2016185DI010.ReferenceTan AT, Yang N, Lee Krishnamoorthy T, et al. Use of Expression Profiles of HBV-DNA Integrated Into Genomes of Hepatocellular Carcinoma Cells to Select T Cells for Immunotherapy. Gastroenterology 2019;156(6):1862–1876.e9.


Hepatology ◽  
1997 ◽  
Vol 26 (4) ◽  
pp. 1027-1034 ◽  
Author(s):  
A Bertoletti ◽  
S Southwood ◽  
R Chesnut ◽  
A Sette ◽  
M Falco ◽  
...  

2003 ◽  
Vol 100 (17) ◽  
pp. 9849-9854 ◽  
Author(s):  
B. Rabe ◽  
A. Vlachou ◽  
N. Pante ◽  
A. Helenius ◽  
M. Kann

Nanoscale ◽  
2018 ◽  
Vol 10 (36) ◽  
pp. 16984-16989 ◽  
Author(s):  
Xinyu Sun ◽  
Dong Li ◽  
Zhaoshuai Wang ◽  
Qiao Liu ◽  
Yinan Wei ◽  
...  

HBV capsid dimorphism regulation through manipulating the rate of capsid nucleation using highly concentrated and/or multivalent counter-cations.


Author(s):  
Lauriane Lecoq ◽  
Maarten Schledorn ◽  
Shishan Wang ◽  
Susanne Smith-Penzel ◽  
Alexander A. Malär ◽  
...  

2006 ◽  
Vol 44 ◽  
pp. S168-S169
Author(s):  
P. Borentain ◽  
P. Colson ◽  
A. Motte ◽  
V. Moa ◽  
M. Henry ◽  
...  

2005 ◽  
Vol 79 (5) ◽  
pp. 3016-3027 ◽  
Author(s):  
Margaret Chen ◽  
Matti Sällberg ◽  
Janice Hughes ◽  
Joyce Jones ◽  
Luca G. Guidotti ◽  
...  

ABSTRACT The function of the hepatitis B virus (HBV) precore or HBeAg is largely unknown because it is not required for viral assembly, infection, or replication. However, the HBeAg does appear to play a role in viral persistence. It has been suggested that the HBeAg may promote HBV chronicity by functioning as an immunoregulatory protein. As a model of chronic HBeAg exposure and to examine the tolerogenic potential of the HBV precore and core (HBcAg) proteins, HBc/HBeAg-transgenic (Tg) mice crossed with T cell receptor (TCR)-Tg mice expressing receptors for the HBc/HBeAgs (i.e., TCR-antigen double-Tg pairs) were produced. This study revealed three phenotypes of HBe/HBcAg-specific T-cell tolerance: (i) profound T-cell tolerance most likely mediated by clonal deletion, (ii) T-cell clonal ignorance, and (iii) nondeletional T-cell tolerance mediated by clonal anergy and dependent on the structure, location, and concentration of the tolerogen. The secreted HBeAg is significantly more efficient than the intracellular HBcAg at eliciting T-cell tolerance. The split T-cell tolerance between the HBeAg and the HBcAg and the clonal heterogeneity of HBc/HBeAg-specific T-cell tolerance may have significant implications for natural HBV infection and especially for precore-negative chronic hepatitis.


2007 ◽  
Vol 14 (12) ◽  
pp. 1623-1628 ◽  
Author(s):  
Odd Odinsen ◽  
Shirley Owusu-Ofori ◽  
Albert Dompreh ◽  
Francis Sarkodie ◽  
Ohene Opare-Sem ◽  
...  

ABSTRACT Antibodies to influenza virus and human immunodeficiency virus are detectable in B cells during the early stages of the immune response, prior to their occurrence in plasma. To investigate similar phenomena in a model of immunization against hepatitis B virus (HBV) infection, medical students in Ghana were screened for HBV markers, HBV surface (HBs) antigen (HBsAg), and HBV core antibodies (anti-HBc). Consenting volunteers, 24 of whom were seronegative (susceptible) and 2 of whom were positive for anti-HBc (prior infection), were vaccinated on day 0, day 40, and 6 months. Two sets of 10 blood samples, sequentially collected at intervals of 2 days following each immunization on days 0 and 40, were processed into B-cell lysates and plasma. Solid-phase HBsAg coated on microtiter plates for enzyme immunoassay or nitrocellulose membranes for dot blot assay was used to detect anti-HBs activity by an indirect antiglobulin assay. A commercially procured sandwich immunoassay was used, along with an enzyme-linked immunosorbent assay and a dot blot assay, for the detection of anti-HBs in B-cell lysates and plasma. Following the first injection of vaccine, a single sample of B-cell lysate collected between 5 and 21 days revealed anti-HBs in 18/21 subjects with no plasma antibodies detectable by sandwich immunoassay. After the booster dose was injected on day 40, a single sample of B-cell lysate collected between 44 and 49 days showed anti-HBs in 16/19 subjects, and this was accompanied by plasma antibodies in 8 subjects. In contrast, between 8 and 13 days, both subjects with prior HBV infection showed anti-HBs in B-cell lysates and plasma. Thus, primary immunization with the HBV vaccine appears to transiently elicit low-affinity anti-HBs in B-cell lysates into plasma.


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