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gp100 is a pigment-cell protein, and the target of the first bispecific drug to improve survival in a solid tumour, uveal melanoma.
gp100 (PMEL) is a melanosomal matrix protein of the pigment-cell lineage, present in more than 90 percent of melanomas including uveal melanoma. It sits inside the cell and is presented on the surface only as peptide in HLA, so it is reached through T-cell receptor recognition rather than antibodies. Tebentafusp (Kimmtrak), an ImmTAC that fuses a high-affinity TCR against gp100/HLA-A*02:01 to an anti-CD3 effector, improved overall survival in metastatic uveal melanoma in the IMCgp100-202 trial, making it the first bispecific to improve survival in a solid tumour. Because normal skin melanocytes also carry gp100, rash is an expected on-target effect, and the HLA-A*02:01 restriction limits eligibility. Extending the approach to cutaneous melanoma is under study. The newcomer's version: gp100 is a pigment-cell protein that gave uveal melanoma its first life-extending drug.
In plain words · gp100 is a pigment-cell protein, and the target of the first bispecific drug to improve survival in a solid tumour, uveal melanoma.
gp100 is a pigment-cell protein, and the target of the first bispecific drug to improve survival in a solid tumour, uveal melanoma.
Melanosomal matrix protein; intracellular, presented on HLA.
1 product aims at gp100 (PMEL): bispecific antibodies. Drugs bind the molecule precisely: to switch it off, flag the cell for the immune system, or deliver a payload.
Tumour-associated overexpression: 1 cell-killing or cell-finding medicine (Tebentafusp) aim at the antigen, which HPA finds stained high in 1 normal tissue; the medicine relies on the tumour carrying more of it than the normal tissue it shares it with. HPA PMEL: RNA tissue enhanced (cervix 32 nTPM, skin 1 109 nTPM); high antibody staining in 1 normal tissue; highest cancer staining melanoma (8 of 12 high). Distribution: 1 cancer family in the corpus carries a prevalence row, label threshold or catalogue link for it (Skin cancer (all types)); Open Targets associates it with 0 specific cancer types at or above 0.5. (Rule 5 of scripts/fetch-target-specificity.ts.)
Sources: Human Protein Atlas PMEL tissue; Human Protein Atlas PMEL pathology; Open Targets ENSG00000185664 associations
First described 1990. Earliest sequence paper UniProt cites for the protein: Vogel, 1990, "Sequence of a melanocyte specific secreted glycoprotein". Source.
Melanosomal matrix protein; intracellular, presented on HLA.
RNA: tissue enhanced (cervix 32 nTPM, skin 1 109 nTPM), detected in many normal tissues.
RNA cancer enriched: Skin Cutaneous Melanoma 7,481 pTPM.
HPA PMEL tissue · HPA PMEL pathology · HPA protein class: FDA approved drug targets
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.
The first drug to improve survival in metastatic uveal melanoma, and the first TCR-based bispecific.
Query for this target: (TITLE:"gp100" OR ABSTRACT:"gp100" OR TITLE:"PMEL" OR ABSTRACT:"PMEL") 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 gp100 (PMEL), 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, Melanoma and the tag tcr-target.
Shares IMCgp100-202, Tebentafusp, Oxford Cancer (Oxford University Hospitals and University of Oxford), Uveal melanoma.
Shares Tebentafusp, TCR-T cell therapy, T-cell engagers (bispecific), Melanoma.
Shares Tebentafusp, TCR-T cell therapy, Antigen presentation & immune editing, Uveal melanoma.
Shares HLA-A, Tebentafusp, Uveal melanoma, Melanoma.
Shares HLA-A, Tebentafusp, Uveal melanoma, T-cell engagers (bispecific).
Shares Tebentafusp, TCR-T cell therapy, T-cell engagers (bispecific), Melanoma.