HLA-A*02:01-presented gp100 peptide (gp209-2M) (HLA-A*02:01/gp100(209-2M))

The target is a peptide-major histocompatibility complex (pMHC) consisting of the HLA-A*02:01 molecule presenting a modified peptide derived from the melanoma-associated antigen gp100, also known as PMEL [1, 2]. The peptide, designated gp209-2M (sequence: IMDQVPFSV), is a synthetic variant of the native gp100(209-217) epitope with a threonine-to-methionine substitution at the second position to increase its binding affinity for the HLA-A*02:01 groove [7, 15]. This complex is specifically recognized by CD8+ T-cell receptors (TCRs), an interaction that is naturally stabilized by the CD8 co-receptor which binds to the alpha-3 domain of the MHC molecule [20]. In clinical practice, this pMHC complex serves as the primary target for tebentafusp (Kimmtrak), a first-in-class bispecific T-cell engager that redirects T cells to kill gp100-expressing melanoma cells [3, 5]. The target is primarily relevant for the treatment of HLA-A*02:01-positive patients with metastatic uveal melanoma, where it has demonstrated significant overall survival benefits [6, 8].

Other names

gp100(209-2M)g209-2MIMDQVPFSVgp100:209-217(210M)HLA-A*02:01-gp100 complexMelanocyte protein PMEL peptide (209-217) mutant

T-cell redirection via bispecific T-cell receptor (TCR) fusion protein