Product pipeline: Preferentially Expressed Antigen in Melanoma (PRAME)

The 509 amino-acids protein PRAME was originally identified as an antigen recognized by an HLA-A24-restricted cytotoxic T lymphocyte (CTL) clone isolated from a melanoma cell line. PRAME is over-expressed in a variety of human cancers, including non-small cell lung, breast, renal cell carcinomas, head and neck cancers, lymphomas, sarcomas, Wilm's tumors and medulloblastomas. It is not expressed in normal tissues, except for testis.

PRAME therefore is a defined TAA (tumor-associated antigen) and an attractive target for anti-tumor immune therapies. To design peptide-based anti-tumor vaccines ISA has identified PRAME-specific epitopes that can initiate anti-tumor T-cell responses. Therefore an effective anti-tumor vaccine should encompass both CTL (MHC class I) and T-helper (MHC class II) epitopes that are also naturally presented after endogenous processing in PRAME-positive cells.

ISA's research & development program on PRAME is focused on the further identification and characterization of PRAME-specific CD8+ and CD4+ T-cell epitopes that can be used in PRAME-specific anti-tumor peptide vaccines. More specifically, for potential CD8+ epitopes identification experiments are performed to analyze:

• the effective binding of the peptide to MHC class I molecules
• liberation of the C-terminus of the peptide by proteasomal cleavage
• immunogenic capacity of the synthetic peptides to induce CTL responses

PRAME is over-expressed in different solid tumor types and hematological malignancies but not or weakly in normal tissues.