T cell receptor recognizing actively personalized vaccine peptide–MHC complexes (TCR-APVAC-pMHC)

The T cell receptor (TCR) recognizing actively personalized vaccine (APVAC) peptide–MHC complexes is a specialized immune receptor responsible for identifying specific tumor antigens presented on the surface of cancer cells. These receptors are central to personalized immunotherapy strategies, such as the GAPVAC (Glioma Actively Personalized VACcine) project, which tailors vaccines to the unique antigenic profile of a patient's tumor (Hilf et al., 2019, Nature). The target involves two types of antigens: APVAC1, which are non-mutated tumor-associated antigens selected from a pre-defined warehouse, and APVAC2, which are patient-specific neoantigens identified through sequencing (NCT02149225). When the TCR binds to its cognate APVAC peptide-MHC complex, it initiates a signaling cascade that activates the T cell, leading to the targeted destruction of malignant cells. This interaction is highly specific and depends on the patient's human leukocyte antigen (HLA) type, typically HLA-A*02 or HLA-A*24, and the specific peptide sequence derived from the tumor. Therapeutic approaches focusing on these TCRs include peptide vaccines designed to expand endogenous T cell populations or the engineering of T cells to express these specific receptors (TCR-T therapy). Understanding the binding affinity and specificity of these TCRs is crucial for maximizing anti-tumor efficacy while minimizing the risk of cross-reactivity with self-antigens in healthy tissues.

Other names

APVAC-specific T cell receptorNeoantigen-specific T cell receptorGAPVAC-associated T cell receptorTumor-infiltrating lymphocyte receptor

The T cell receptor binds to specific peptide-MHC complexes presented on the surface of tumor cells, triggering a signaling cascade through the CD3 complex that leads to T cell proliferation, cytokine release, and granzyme-mediated apoptosis of the target cell.