Virus-infected cells presenting Epstein-Barr virus, cytomegalovirus, BK polyomavirus, or adenovirus antigens (Multi-VST targets)

The target consists of host cells infected with Epstein-Barr virus (EBV), cytomegalovirus (CMV), BK polyomavirus (BKV), or adenovirus (AdV) that present viral peptides on their surface via Major Histocompatibility Complex (MHC) molecules [1, 4, 15]. These cells are primarily found in immunocompromised patients, such as those undergoing hematopoietic stem cell transplantation (HSCT) or solid organ transplantation (SOT), where the lack of endogenous T-cell immunity allows for viral reactivation or primary infection [1, 12]. Therapeutic strategies targeting these cells involve the adoptive transfer of multi-virus specific T-cells (multi-VSTs), which are expanded to recognize specific immunodominant viral antigens such as CMV pp65, EBV EBNA1, AdV Hexon, and BKV Large T-antigen [6, 15]. Upon recognition of the peptide-MHC complex by the T-cell receptor (TCR), the VSTs exert cytotoxic effects, including the release of perforin and granzymes, to eliminate the infected cells and reduce viral load [2, 6]. This approach aims to restore protective immunity and treat refractory viral diseases like BKV-associated hemorrhagic cystitis or EBV-related lymphoproliferative disorders [1, 13]. Clinical development of drugs like posoleucel has focused on providing an off-the-shelf, partially HLA-matched solution for these life-threatening infections [1, 9].

Other names

Multi-virus specific T-cell targetsViral antigens (EBV, CMV, BKV, AdV)Post-transplant viral antigensMHC-presented viral peptides

Adoptive T-cell therapy; recognition of viral peptide-MHC complexes by T-cell receptors (TCRs) leading to cytotoxic lysis of infected cells.