Polyclonal T-cell receptor (TCR)

Polyclonal T-cell receptors (TCRs) are highly diverse protein complexes on the surface of T-lymphocytes that mediate the recognition of specific antigens presented by Major Histocompatibility Complex (MHC) molecules [1]. In oncology, these receptors are directed toward patient-specific neoantigens or tumor-associated antigens (TAAs) that are processed and presented by professional antigen-presenting cells, such as dendritic cells, to prime the immune system [2]. Unlike monoclonal approaches, a polyclonal TCR population provides a broad-spectrum immune response capable of addressing tumor heterogeneity and reducing the risk of immune escape through antigen loss [2,4]. Therapeutic strategies leveraging these receptors include Tumor-Infiltrating Lymphocyte (TIL) therapy, such as Lifileucel, and personalized neoantigen vaccines like mRNA-4157, which aim to expand or induce a robust, multi-target T-cell repertoire [3,4]. Upon binding to their cognate peptide-MHC ligand, these TCRs trigger intracellular signaling cascades that lead to T-cell proliferation, the secretion of pro-inflammatory cytokines, and the targeted destruction of malignant cells [1]. This target is fundamental to the efficacy of modern personalized immunotherapies, particularly in treating advanced solid tumors where broad recognition of the evolving tumor landscape is required [3,4].

Other names

Neoantigen-specific T-cell receptorTumor-reactive T-cell receptorAntigen-specific TCRTumor-infiltrating lymphocyte receptorPolyclonal TCR repertoire

Recognition of peptide-major histocompatibility complex (pMHC) on antigen-presenting cells or tumor cells, triggering T-cell expansion, cytokine release, and direct lysis of target cells.