Viral Peptide-Major Histocompatibility Complexes (Adenovirus, Cytomegalovirus, Epstein-Barr Virus) (pMHC (Adv/CMV/EBV))

The target consists of specific viral peptide fragments presented by Major Histocompatibility Complex (MHC) molecules on the surface of cells infected with Adenovirus, Cytomegalovirus (CMV), or Epstein-Barr Virus (EBV) [1]. These epitopes are derived from immunodominant viral proteins, including Hexon and Penton from Adenovirus, IE1 and pp65 from CMV, and EBNA1, LMP2, and BZLF1 from EBV [2]. In healthy individuals, these peptide-MHC (pMHC) complexes are recognized by the endogenous T-cell repertoire, maintaining viral latency or clearing acute infection [3]. However, in immunocompromised patients, such as those undergoing hematopoietic stem cell transplantation (HSCT), the absence of effective T-cell surveillance allows for viral reactivation and life-threatening complications [1, 4]. Therapeutic interventions like posoleucel (ALVR105) utilize donor-derived, multi-virus-specific T cells that target these pMHC complexes to restore cellular immunity [1, 5]. By binding to these specific viral signatures, the therapeutic T cells induce targeted lysis of infected cells and release pro-inflammatory cytokines to coordinate a broader immune response [2, 4]. This approach provides a broad-spectrum antiviral effect against multiple co-infecting pathogens common in the post-transplant setting [1]. Citations: [1] Tzannou I, et al. J Clin Oncol. 2017;35(31):3547-3557. [2] Leen AM, et al. Blood. 2013;121(26):5113-5123. [3] Withers B, et al. Curr Opin Hematol. 2017;24(6):476-483. [4] O'Reilly RJ, et al. Immunol Res. 2011;49(1-3):227-242. [5] Allovir. "Posoleucel (ALVR105) Product Profile." 2023.

Other names

Multi-virus specific T-cell targetsViral pMHC complexesHLA-restricted viral epitopesAdenovirus/CMV/EBV peptide-MHC

T-cell receptor (TCR) mediated recognition of viral peptide-MHC complexes leading to cytotoxic T-lymphocyte (CTL) activation and lysis of infected cells.