Preferentially expressed antigen in melanoma-specific T cell receptor (PRAME-TCR) (PRAME-TCR)

The PRAME-specific T cell receptor (TCR) is a specialized immune receptor, often engineered for use in adoptive T-cell therapies, that targets the Preferentially Expressed Antigen in Melanoma (PRAME) [1]. PRAME is a member of the cancer-testis antigen family, characterized by high expression in various malignancies—including melanoma, lung cancer, and sarcomas—while remaining largely absent in healthy adult tissues, except for the immune-privileged testis [2]. The TCR is designed to recognize specific PRAME-derived peptide fragments, such as the SLLQHLIGL epitope, when presented by Major Histocompatibility Complex (MHC) molecules, typically HLA-A*02:01 [3]. When an engineered T cell expressing this TCR encounters a PRAME-presenting tumor cell, the receptor-ligand interaction triggers T-cell activation, leading to the release of cytotoxic granules and cytokines to eliminate the cancer cell [4]. This mechanism allows for the targeting of intracellular proteins that are processed and presented on the cell surface, a significant advantage over traditional CAR-T therapies that only recognize surface antigens [2]. Clinical development of PRAME-specific TCR-T therapies, such as IMA203, has shown promising anti-tumor activity and a manageable safety profile in patients with heavily pretreated solid tumors [5]. These therapies are currently being investigated for their potential to provide durable responses in cancers that have failed standard-of-care treatments [3]. The specificity of the TCR for the PRAME-HLA complex is critical to minimizing off-target effects and ensuring therapeutic efficacy [1].

Other names

PRAME TCRPRAME-directed T-cell receptorT-cell receptor specific for PRAMEPRAME-specific TCR

Engineered T cells expressing the PRAME-specific TCR recognize and bind to PRAME peptide-HLA complexes (typically HLA-A*02:01) on the surface of tumor cells, initiating a signaling cascade that results in T cell proliferation, cytokine production, and direct cytotoxic lysis of the target cell [3, 4].