Frameshift-derived neoantigen peptides presented by MHC on autologous dendritic cells (FSP-DC)

Frameshift-derived neoantigen peptides are novel amino acid sequences created by genomic insertions or deletions that alter the reading frame of a gene, a phenomenon frequently observed in cancers with microsatellite instability (MSI) (Kloor & von Knebel Doeberitz, 2016). Because these sequences are entirely absent from the normal human proteome, they are perceived as "non-self" by the immune system, making them highly potent targets for immunotherapy with minimal risk of central tolerance (Roudko et al., 2021). When these peptides are loaded onto autologous dendritic cells and presented via Major Histocompatibility Complex (MHC) molecules, they function as a personalized vaccine to prime and activate the patient's own T cells. This process specifically induces the expansion of CD8+ cytotoxic T lymphocytes and CD4+ helper T cells capable of recognizing and destroying tumor cells that express these unique frameshift mutations (Mandal et al., 2019). This therapeutic approach is primarily investigated for mismatch repair-deficient (dMMR) and MSI-high (MSI-H) tumors, including colorectal, gastric, and endometrial cancers, as well as in the context of Lynch syndrome (NCT03639714). By utilizing autologous dendritic cells, the therapy ensures that the antigen presentation is perfectly matched to the patient's human leukocyte antigen (HLA) type, optimizing the immune response. Clinical trials are currently evaluating the efficacy of these neoantigen-pulsed dendritic cells both as monotherapies and in combination with immune checkpoint inhibitors to enhance anti-tumor activity and provide long-term immunological memory.

Other names

Frameshift-derived neoantigensFSP-loaded dendritic cellsNeoantigen-pulsed autologous dendritic cellsFrameshift mutation-derived peptidesFSP-MHC complex

Induction of tumor-specific T-cell immunity through the presentation of non-self peptides by autologous antigen-presenting cells to prime cytotoxic and helper T-cell responses.