Cytomegalovirus phosphoprotein 65 peptide–Major Histocompatibility Complex (CMV pp65–MHC)

The Cytomegalovirus phosphoprotein 65 (pp65) peptide–Major Histocompatibility Complex (MHC) is a specialized immunological target found on the surface of certain tumor cells, most notably in glioblastoma multiforme (GBM) (Cobbs et al., 2002, Cancer Res). While CMV is a common latent virus, its proteins like pp65 (encoded by the UL83 gene) are frequently expressed within the tumor microenvironment while remaining absent in healthy surrounding tissues (Prins et al., 2008, Neuro Oncol). These proteins are processed into short peptides and presented by MHC Class I molecules, creating a unique signature for immune recognition (Schuessler et al., 2014, Clin Cancer Res). This complex serves as a highly specific target for various immunotherapies, including TCR-engineered T cells and peptide-based vaccines like VBI-1901 (Nair et al., 2014, Clin Cancer Res; VBI Vaccines). By targeting the pp65-MHC complex, these therapies aim to induce a potent and selective cytotoxic T-cell response against malignant cells. Clinical development focuses on leveraging this viral-derived antigen to overcome the low mutational burden and immunosuppressive nature of certain solid tumors (Batich et al., 2017, Clin Cancer Res).

Other names

CMV pp65-HLA complexHLA-A*02:01/pp65(495–503)CMV pp65 antigen-MHC complexUL83 peptide-MHC complexpp65-HLA-A2 complex

Recognition of the peptide-MHC complex by specific T-cell receptors (TCRs) triggers the activation of cytotoxic T lymphocytes, leading to the targeted lysis of cells expressing the viral antigen (Schuessler et al., 2014, Clin Cancer Res).