T-cell receptor on UV1-specific CD4+ T cells (UV1-specific TCR)

T-cell receptors (TCRs) on UV1-specific CD4+ T cells are specialized protein complexes that recognize peptide fragments of human telomerase reverse transcriptase (hTERT) presented by MHC class II molecules [Ultimovacs, 2024]. hTERT is a nearly universal tumor antigen, expressed in over 85% of all cancers, where it enables replicative immortality by maintaining telomere length [Inderberg et al., 2022]. The UV1 vaccine is a therapeutic peptide vaccine composed of three long hTERT peptides designed to stimulate the expansion of CD4+ T cells bearing these specific TCRs [Ellingsen et al., 2021]. When these TCRs bind to their cognate hTERT epitopes, they trigger a Th1-polarized immune response, leading to the secretion of pro-inflammatory cytokines such as interferon-gamma (IFN-gamma) and tumor necrosis factor (TNF) [Inderberg et al., 2022]. These cytokines help to remodel the tumor microenvironment and activate cytotoxic CD8+ T cells, facilitating a robust anti-tumor attack. This mechanism is currently being leveraged in clinical trials combining UV1 with immune checkpoint inhibitors like pembrolizumab and ipilimumab to overcome tumor-induced immunosuppression in patients with melanoma and mesothelioma [NCT04300244; NCT03438591]. Because hTERT is minimally expressed in most normal adult tissues, these TCRs provide a high degree of specificity for malignant cells, minimizing off-target toxicity [Ellingsen et al., 2021].

Other names

hTERT-specific T-cell receptorUV1-reactive TCRTelomerase-specific T-cell receptorhTERT-reactive CD4+ T-cell receptor

The UV1 vaccine provides long synthetic peptides from human telomerase reverse transcriptase (hTERT) that are processed and presented by MHC class II molecules. This stimulates the expansion and activation of CD4+ T cells expressing TCRs specific for these hTERT epitopes. Upon recognition of hTERT on tumor cells or antigen-presenting cells, these TCRs trigger a Th1-polarized immune response, characterized by the secretion of interferon-gamma (IFN-gamma) and tumor necrosis factor (TNF), which orchestrates a multi-faceted anti-tumor attack [Inderberg et al., 2022; Ultimovacs, 2024].