Absent in melanoma 2 (AIM2) frameshift peptide antigen (AIM2-FSP)

The Absent in melanoma 2 (AIM2) frameshift peptide antigen is a tumor-specific neoantigen generated by a recurrent mutation in cancers with microsatellite instability (MSI) (Schwitalle et al., 2008). In MSI-high (MSI-H) tumors, such as colorectal and gastric cancers, the deficiency in DNA mismatch repair leads to a characteristic 1-base pair deletion in the (A)10 coding microsatellite tract of the AIM2 gene (Tougeron et al., 2012). This mutation results in a translational frameshift that produces a novel, highly immunogenic C-terminal peptide sequence not found in normal tissues. This frameshift peptide (FSP) is processed and presented on the cell surface by MHC molecules, where it can be recognized by CD8+ and CD4+ T cells (D'Alise et al., 2022). Because the AIM2 mutation is a frequent and early event in MSI-H oncogenesis, it serves as a shared neoantigen for off-the-shelf immunotherapy. Therapeutic candidates like the Nous-209 vaccine incorporate the AIM2-FSP to stimulate a broad and durable anti-tumor immune response (D'Alise et al., 2020).

Other names

AIM2-fsAIM2 frameshift neoantigenAIM2 (A)10 frameshift peptideAbsent in melanoma 2 mutation-derived neoantigen

Active immunization to induce T-cell mediated cytotoxicity against cells expressing the frameshifted AIM2 protein.