Patient-specific human leukocyte antigen class I-peptide complex (APVAC1) (HLA-I/APVAC1)

Patient-specific human leukocyte antigen (HLA) class I molecules presenting APVAC1-derived tumor-associated peptides are personalized molecular targets used in cancer immunotherapy, specifically for glioblastoma (Hilf et al., 2019, Nature). These targets consist of a complex between a patient's specific HLA class I allele and a non-mutated tumor-associated peptide (TUMAP) selected from a pre-defined library. The APVAC1 (Actively Personalized VACcine 1) approach utilizes a "warehouse" of peptides that are frequently overexpressed in tumor tissue but have low expression in healthy organs (NCT02149225). By identifying which of these peptides are present in a specific patient's tumor through mass spectrometry and RNA sequencing, a tailored vaccine is created to induce a targeted immune response. Once the vaccine peptides are presented by HLA class I molecules on the cell surface, they serve as ligands for the T-cell receptors of CD8+ cytotoxic T lymphocytes. This interaction triggers the activation and proliferation of T cells, which then recognize and destroy tumor cells displaying the same HLA-peptide complexes. This strategy is particularly relevant for "cold" tumors with low mutational burdens, where neoantigen targets are scarce. Clinical trials like GAPVAC-101 have shown that targeting these complexes can successfully induce sustained T-cell responses in patients with newly diagnosed glioblastoma.

Other names

HLA-I/TUMAP complexMHC class I-peptide complexAPVAC1-derived peptide-HLA complexGAPVAC APVAC1 targetHuman leukocyte antigen class I-tumor associated peptide complex

The target functions as a ligand for CD8+ T-cell receptors; the therapeutic vaccine (APVAC1) provides the peptides that form these complexes to stimulate a specific cytotoxic T-cell response against tumor cells.