Cancer-Testis Antigens (CTA) and Oncofetal Antigens (OFA) (CTA/OFA)

Retired self-proteins refers to a class of tumor-associated antigens, primarily Cancer-Testis Antigens (CTAs) and Oncofetal Antigens, which are normally expressed during embryonic development or in germ cells but are silenced in healthy adult tissues (Gnjatic et al., 2006; StatPearls). In ovarian cancer, these proteins are frequently re-expressed due to epigenetic dysregulation, making them ideal targets for immunotherapy as the immune system perceives them as foreign in the context of adult somatic tissue (Thomas et al., 2023). These antigens are considered self-proteins because they are encoded by the host genome, but they are retired in the sense that their physiological expression is restricted to specific developmental windows (OSE Immunotherapeutics). Therapeutic strategies targeting these proteins, such as the neoepitope vaccine Tedopi (OSE-2101), utilize specific peptide sequences to prime cytotoxic T-lymphocytes to recognize and destroy cancer cells (OSE Immunotherapeutics). Because these proteins are generally absent from vital adult organs, they offer a wide therapeutic window with a low risk of systemic autoimmunity (NCI). However, the primary challenge in targeting these proteins is the heterogeneity of their expression within the tumor, which can lead to immune evasion and treatment resistance (Thomas et al., 2023).

Other names

Retired self-proteinsCancer-testis antigensOncofetal antigensTumor-associated antigensTAAsNeoepitopes

Induction of a multi-epitope cytotoxic T-lymphocyte (CTL) response against tumor cells re-expressing developmental or germline-specific proteins.