CD3 and PRAME peptide-MHC complex (CD3/PRAME-MHC)

The CD3 and PRAME peptide-MHC complex is a dual therapeutic target utilized in bispecific T-cell redirection therapies, such as ImmTACs (Immune mobilizing monoclonal TCRs Against Cancer) and T-cell engagers (TCEs). PRAME (Preferentially expressed Antigen in Melanoma) is a cancer-testis antigen that is highly overexpressed in a variety of solid and hematological malignancies but has restricted expression in normal adult tissues, primarily the testes and ovaries [4, 12]. In this target configuration, a specific PRAME-derived peptide (commonly the HLA-A*02:01-restricted SLLQHLIGL) is presented on the tumor cell surface by Major Histocompatibility Complex (MHC) class I molecules [2, 14]. Bispecific drugs are engineered to simultaneously bind this peptide-MHC complex and the CD3 epsilon subunit of the T-cell receptor (TCR) on cytotoxic T lymphocytes [1, 5]. This dual engagement bypasses the need for natural TCR-antigen recognition, effectively "bridging" the T cell to the tumor cell and triggering a potent, localized immune response that leads to tumor cell lysis [2, 10]. Clinical development of agents like brenetafusp (IMC-F106C) has demonstrated that targeting this complex can induce robust T-cell infiltration and objective clinical responses in patients with high PRAME expression and the appropriate HLA genotype [8, 11].

Other names

PRAME-HLA-A*02:01/CD3PRAME x CD3PRAME-MHC/CD3 complexPRAME-pHLA/CD3

T-cell redirection and activation via bridging the CD3 epsilon subunit on T cells and PRAME peptide-MHC complexes on tumor cells, leading to the formation of an immunological synapse and subsequent T-cell-mediated tumor cell lysis.