Mutant Von Hippel-Lindau tumor suppressor protein-derived neoantigen-HLA complex (Mutant VHL-HLA complex)

The target consists of specific peptide fragments derived from mutated Von Hippel-Lindau (VHL) tumor suppressor protein, which are processed and presented on the cell surface by Human Leukocyte Antigen (HLA) molecules [1]. In clear cell renal cell carcinoma (ccRCC), VHL mutations are nearly ubiquitous, often resulting in frameshifts or point mutations that generate novel amino acid sequences, known as neoantigens, not present in healthy tissue [2]. These mutant VHL-HLA complexes serve as highly specific markers for malignant cells, enabling the development of T-cell receptor (TCR) based therapies and vaccines designed to trigger a selective immune response [3]. Because the wild-type VHL protein does not produce these specific peptide sequences, therapies targeting these complexes minimize off-target effects on normal cells [4]. The effectiveness of this target is highly dependent on the patient's specific HLA allele and the presence of the corresponding VHL mutation, necessitating a personalized medicine approach [5]. Current research focuses on identifying high-affinity TCRs that can recognize these complexes to treat advanced renal cancers [6]. Sources: [1] Gnarra et al., Nature Genetics (1994); [2] Gossage et al., Nature Reviews Cancer (2015); [3] Schumacher & Schreiber, Science (2015); [4] Robbins et al., Nature Medicine (2013); [5] Ott et al., Nature (2017); [6] Smith et al., Journal for ImmunoTherapy of Cancer (2021).

Other names

VHL neoantigenMutant VHL peptide-MHC complexVHL-derived neoepitopeVHL-HLA neoantigen

T-cell receptor-mediated recognition and cytotoxic T-lymphocyte activation