Molecular features of the hepatitis B virus nucleocapsid T-cell epitope 18-27: Interaction with HLA and T-cell receptor

Hepatology ◽  
1997 ◽  
Vol 26 (4) ◽  
pp. 1027-1034 ◽  
Author(s):  
A Bertoletti ◽  
S Southwood ◽  
R Chesnut ◽  
A Sette ◽  
M Falco ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
T Cell ◽  
Hepatitis B ◽  
T Cell Receptor ◽  
Cell Epitope ◽  
Cell Receptor ◽  
T Cell Epitope ◽  
Molecular Features ◽  
B Virus

272 Use of LioCyx-M, autologous hepatitis B virus (HBV)-Specific T cell receptor (TCR) T-cells, in advanced HBV-related hepatocellular carcinoma (HCC)

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A297-A297
Author(s):  
Fu-Sheng Wang ◽  
Fanping Meng ◽  
Jiehua Jin ◽  
Yuanyuan Li ◽  
Regina Wanju Wong ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Hepatitis B Virus ◽  
T Cell ◽  
Hepatitis B ◽  
T Cell Receptor ◽  
Dose Level ◽  
Cell Receptor ◽  
Hbv Dna ◽  
B Virus

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.

scholarly journals Naturally Occurring Hepatitis B Virus B-Cell and T-Cell Epitope Mutants in Hepatitis B Vaccinated Children

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Yu-Min Lin ◽  
Guey-Mei Jow ◽  
Shu-Chi Mu ◽  
Bing-Fang Chen
Keyword(s):  
Hepatitis B Virus ◽  
T Cell ◽  
Hepatitis B ◽  
B Cell ◽  
Cell Epitope ◽  
Hbv Infection ◽  
Core Antigen ◽  
T Cell Epitope ◽  
Naturally Occurring ◽  
B Virus

To control hepatitis B virus (HBV) infection, a universal HBV vaccination program for infants was launched in Taiwan in 1984. The aim of this study was to investigate the role of B-cell and T-cell epitope variations of HBsAg and polymerase in HBV infection in vaccinated children. One hundred sixty-three sera from vaccinated children were enrolled randomly. HBV serum markers, including hepatitis B surface antigen (HBsAg) and antibodies to HBsAg (anti-HBs) and core antigen (anti-HBc), were detected by ELISA. Nucleotide sequences encoding the S and the pre-S regions of HBsAg were analyzed in all HBsAg positive sera. Five children were HBsAg positive. Sequence analysis of S, pre-S, and overlapped polymerase (P) genes showed that HBV isolates of HBsAg-positive vaccinees were variants; no G145R but G145A and other substitutions were found in the “a” determinant. Fifteen, six, and eight amino acid substitutions within B-cell and T-cell epitopes of S, pre-S, and P regions were detected, respectively. Several immune-epitope mutants, such as S45T/A, N131T, I194V, and S207N in S, were detected in all isolates. In conclusion, our results suggested that these naturally occurring immunoepitope mutants, which changed their immunogenicity leading to escape from immune response, might cause HBV infection.

scholarly journals Targeting Hepatitis B Virus-Infected Cells with a T-Cell Receptor-Like Antibody

2010 ◽  
Vol 85 (5) ◽  
pp. 1935-1942 ◽  
Author(s):  
K. S. R. Sastry ◽  
C. T. Too ◽  
K. Kaur ◽  
A. J. Gehring ◽  
L. Low ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
T Cell ◽  
Hepatitis B ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
B Virus ◽  
Infected Cells

scholarly journals T cell receptor grafting allows virological control of hepatitis B virus infection

2019 ◽  
Vol 129 (7) ◽  
pp. 2932-2945 ◽  
Author(s):  
Karin Wisskirchen ◽  
Janine Kah ◽  
Antje Malo ◽  
Theresa Asen ◽  
Tassilo Volz ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
T Cell ◽  
Virus Infection ◽  
Hepatitis B ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Hepatitis B Virus Infection ◽  
B Virus

scholarly journals Definition of a minimal optimal cytotoxic T-cell epitope within the hepatitis B virus nucleocapsid protein.

1993 ◽  
Vol 67 (4) ◽  
pp. 2376-2380 ◽  
Author(s):  
A Bertoletti ◽  
F V Chisari ◽  
A Penna ◽  
S Guilhot ◽  
L Galati ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
T Cell ◽  
Hepatitis B ◽  
Nucleocapsid Protein ◽  
Cell Epitope ◽  
Cytotoxic T Cell ◽  
T Cell Epitope ◽  
B Virus ◽  
Definition Of

T-Cell Receptor Grafting allows Control of Hepatitis B Virus Infection

2019 ◽  
Author(s):  
K Wisskirchen ◽  
J Kah ◽  
A Malo ◽  
T Asen ◽  
TK Volz ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
T Cell ◽  
Virus Infection ◽  
Hepatitis B ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Hepatitis B Virus Infection ◽  
B Virus

Dynamic changes of T cell receptor repertoires in patients with hepatitis B virus-related acute-on-chronic liver failure

2019 ◽  
Vol 14 (1) ◽  
pp. 47-56 ◽  
Author(s):  
Guojun Shen ◽  
Shuilin Sun ◽  
Jie Huang ◽  
Haohui Deng ◽  
Ying Xu ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
T Cell ◽  
Hepatitis B ◽  
Liver Failure ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Chronic Liver ◽  
Chronic Liver Failure ◽  
Dynamic Changes ◽  
B Virus
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