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Project
INVISIBLE: Investigation and inhibition of Epstein-Barr Virus immune evasion by BILF1-modulating nanobodies (FWOTM1119)
The Epstein-Barr Virus (EBV) is a herpesvirus that has infected
around 90% of the worldwide population. Although primary EBV
infections are usually asymptomatic in healthy individuals, EBV has
been found in several cancers including B cell lymphomas. While the
exact role of EBV in these tumors is not fully understood, EBV
infection is suggested to result in a more immunosuppressive tumor
microenvironment (TME) allowing viral and cancer persistence.
Interestingly, herpesviruses, including EBV, encode for G proteincoupled receptors (GPCRs) in their genome. These viral GPCRs play
an important role in the viral lifecycle by hijacking host cellular
pathways and by promoting immune evasion and exacerbating
pathologies including cancer growth. EBV encodes for one viral
GPCR, BILF1, which has been detected in EBV+ cancer tissue
samples and cell lines. Several studies have shown that BILF1 plays
a role in immune evasion. However, the molecular mechanisms
underlying the immunomodulatory activities by BILF1 and the
consequences of this on the TME have not been investigated. In this
project, we aim to gain more insight in the specific role of BILF1
during (viral) immune evasion and its effect on the TME and
immunotherapy effectivity. Moreover, we will generate BILF1-
targeting nanobodies that will serve as research tools and potential
therapeutics. Overall, this project will serve as a basis to further
investigate the exact role and therapeutic potential of BILF1 in a
cancer setting
around 90% of the worldwide population. Although primary EBV
infections are usually asymptomatic in healthy individuals, EBV has
been found in several cancers including B cell lymphomas. While the
exact role of EBV in these tumors is not fully understood, EBV
infection is suggested to result in a more immunosuppressive tumor
microenvironment (TME) allowing viral and cancer persistence.
Interestingly, herpesviruses, including EBV, encode for G proteincoupled receptors (GPCRs) in their genome. These viral GPCRs play
an important role in the viral lifecycle by hijacking host cellular
pathways and by promoting immune evasion and exacerbating
pathologies including cancer growth. EBV encodes for one viral
GPCR, BILF1, which has been detected in EBV+ cancer tissue
samples and cell lines. Several studies have shown that BILF1 plays
a role in immune evasion. However, the molecular mechanisms
underlying the immunomodulatory activities by BILF1 and the
consequences of this on the TME have not been investigated. In this
project, we aim to gain more insight in the specific role of BILF1
during (viral) immune evasion and its effect on the TME and
immunotherapy effectivity. Moreover, we will generate BILF1-
targeting nanobodies that will serve as research tools and potential
therapeutics. Overall, this project will serve as a basis to further
investigate the exact role and therapeutic potential of BILF1 in a
cancer setting
Date:1 Nov 2022 → Today
Keywords:Epstein-Barr-virus, Nanobodies, Viral G protein-coupled receptors
Disciplines:Biopharmaceuticals, Cancer therapy, Cell signalling, Virology