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PRAME is a cancer-testis antigen: a protein normally confined to the testis that about 90% of cutaneous melanomas and substantial fractions of ovarian, lung, endometrial and uveal cancers switch on. Because it sits inside the cell, drugs reach it only as peptide fragments displayed on HLA, through T-cell receptor bispecifics such as brenetafusp and TCR-T cells such as IMA203.
Preferentially Expressed Antigen in Melanoma is a cancer-testis antigen expressed in ~90% of cutaneous melanomas and in substantial fractions of ovarian, lung, endometrial, and uveal cancers. Intracellular, so reachable only via peptide-HLA recognition: brenetafusp (ImmTAC), IMA203 (Immatics TCR-T, phase 3 in melanoma), and other TCR programmes. PRAME immunohistochemistry is also a diagnostic aid for distinguishing melanoma from naevi.
In plain words · PRAME is a cancer-testis antigen: a protein normally confined to the testis that about 90% of cutaneous melanomas and substantial fractions of ovarian, lung, endometrial and uveal cancers switch on. Because it sits inside the cell, drugs reach it only as peptide fragments displayed on HLA, through T-cell receptor bispecifics such as brenetafusp and TCR-T cells such as IMA203.
PRAME is a cancer-testis antigen: a protein normally confined to the testis that about 90% of cutaneous melanomas and substantial fractions of ovarian, lung, endometrial and uveal cancers switch on. Because it sits inside the cell, drugs reach it only as peptide fragments displayed on HLA, through T-cell receptor bispecifics such as brenetafusp and TCR-T cells such as IMA203.
Represses retinoic acid receptor signalling; drives proliferation and blocks differentiation; presented on HLA class I as peptides such as PRAME 425-433 on A*02:01.
2 products aim at PRAME: bispecific antibodies and cell therapies. Drugs bind the molecule precisely: to switch it off, flag the cell for the immune system, or deliver a payload.
Tumour-associated overexpression: HPA finds the RNA cancer enhanced in cancer (Skin Cutaneous Melanoma (TCGA)) and tissue enriched in normal testis, so the tumour and the normal tissue it comes from share the target and the medicine relies on the difference in level. HPA PRAME: RNA tissue enriched (testis 102 nTPM); high antibody staining in 1 normal tissue. Distribution: 4 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Skin cancer (all types), Ovarian cancer, Lung cancer (all types), Sarcomas (soft tissue, bone, GIST)); Open Targets associates it with 0 specific cancer types at or above 0.5. (Rule 7 of scripts/fetch-target-specificity.ts.)
Sources: Human Protein Atlas PRAME tissue; Human Protein Atlas PRAME pathology; Open Targets ENSG00000185686 associations
First described 1997. Earliest sequence paper UniProt cites for the protein: Ikeda et al, Immunity, 1997, "Characterization of an antigen that is recognized on a melanoma showing partial HLA loss by CTL expressing an NK inhibitory receptor". Source.
Represses retinoic acid receptor signalling; drives proliferation and blocks differentiation; presented on HLA class I as peptides such as PRAME 425-433 on A*02:01.
RNA: tissue enriched (testis 102 nTPM), detected in some normal tissues.
RNA cancer enhanced: Skin Cutaneous Melanoma 193 pTPM.
No cancer stained high; medium in melanoma.
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
Brenetafusp is a soluble T-cell receptor bispecific, tebentafusp's successor, that recognises a PRAME peptide on HLA-A*02:01 and drags T cells onto the tumour. A phase 3 with nivolumab in first-line melanoma is enrolling, but only patients carrying HLA-A*02:01, about half of those of European ancestry, are eligible.
IMA203 is an experimental TCR-T cell therapy from Immatics US in phase 3 trials for melanoma, aimed at PRAME.
Query for this target: (TITLE:"PRAME" OR ABSTRACT:"PRAME") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about PRAME, not a curated reading list.
Shares HLA-A, TCR-T cell therapy, Antigen presentation & immune editing, Uveal melanoma and the tag tcr-target.
Shares HLA-A, TCR-T cell therapy, Antigen presentation & immune editing, Sarcomas (soft tissue, bone, GIST) and the tag tcr-target.
Shares Uveal melanoma prognostic markers (GNAQ/GNA11, monosomy 3, gene-expression class), TCR therapeutics for non-HLA-A*02 patients, Immunocore, HLA-A*02:01 restriction.
Shares IMA203, Immatics, Advanced melanoma (unresectable stage III and stage IV), Melanoma.
Shares Uveal melanoma prognostic markers (GNAQ/GNA11, monosomy 3, gene-expression class), HLA-A*02:01 restriction, HLA-A, Uveal melanoma.
Shares Immunocore, TCR-T cell therapy, Advanced melanoma (unresectable stage III and stage IV), T-cell engagers (bispecific).
Shares Immatics, Immunocore, TCR-T cell therapy, T-cell engagers (bispecific).
Shares Immunocore, Brenetafusp, T-cell engagers (bispecific).