Rhophilin-associated tail protein 1-derived peptide presented on Major Histocompatibility Complex (ROPN1/MHC)

Rhophilin-associated tail protein 1 (ROPN1) is a cancer-testis antigen (CTA) that is normally expressed in the testis and ciliated cells but is frequently overexpressed in various malignancies, including multiple myeloma and triple-negative breast cancer. As a therapeutic target, ROPN1 is processed intracellularly into short peptides that are subsequently presented on the cell surface by Major Histocompatibility Complex (MHC) molecules, most commonly HLA-A*02:01. This peptide-MHC complex serves as a highly specific signature for immune recognition, allowing engineered T-cell receptor (TCR) therapies or TCR-like antibodies to distinguish malignant cells from healthy non-germline tissues. Because ROPN1 expression is largely restricted to immune-privileged sites like the testis, targeting its MHC-presented peptides offers a promising window for potent anti-tumor activity with minimized systemic toxicity. Current drug development efforts focus on utilizing this complex to direct adoptive cell transfers or bispecific engagers toward refractory tumors that lack traditional surface markers.

Other names

ROPN1 peptide-HLA complexRhophilin-associated tail protein 1Cancer-testis antigen 91CT91ROPN1-derived peptide-MHC complex

Recognition of the specific ROPN1 peptide-MHC complex by engineered T-cell receptors (TCRs) or TCR-like molecules, leading to targeted lysis of tumor cells expressing the antigen.