ISA103 is derived from the human antigen PRAME (PReferentially expressed Antigen in MElanoma) and is useful for the treatment of different type of cancers. ISA103 consists of several Synthetic Long Peptides (SLP®) spanning the most immunogenic regions of the protein.

PRAME is expressed on various types of tumors, like lung, breast, head & neck and kidney cancer, as well as melanoma, neuroblastoma and medullablastoma. Expression of PRAME on healthy tissue is very limited and very low and resembles that of Cancer Testis Antigens.

In addition, there also seems to be a functional association of PRAME expression and tumorigenesis. Overexpression of PRAME is associated with a poor prognosis, amongst others in patients with breast cancer, juvenile neuroblastoma and myeloid leukemia. This may be attributed to the function of PRAME as an inhibitor of the retinoic acid receptor, which plays an important role in proliferation arrest, differentiation and apoptosis of cells.

The tumor-specific expression and association with proliferation makes PRAME attractive to develop an immunotherapy for multiple indications. PRAME-expressing cancer cells are not able to escape from PRAME-directed cell-mediated immunity, unless the cells down-regulate PRAME expression, which in turn decreases their aggressiveness. ISA103 is currently in preclinical development.