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

Absent in melanoma 2 (AIM2) frameshift peptide antigens are novel neoantigens generated by specific mutations in the AIM2 gene, frequently observed in cancers with microsatellite instability-high (MSI-H) phenotypes, such as colorectal, gastric, and endometrial carcinomas (PMID: 11507052). These mutations typically occur in a poly-adenosine (A10) tract, resulting in a frame shift that produces a truncated protein with a unique, non-self C-terminal amino acid sequence (PMID: 32690954). These frameshift peptides are processed by the proteasome and presented on the cell surface by Major Histocompatibility Complex (MHC) Class I molecules, where they can be recognized by the host's immune system as foreign (PMID: 33073218). Because these mutations are highly recurrent across different patients with MSI-H tumors, they serve as shared neoantigens, making them ideal targets for off-the-shelf cancer vaccines and T-cell receptor (TCR) based therapies. Therapeutic strategies, such as the Nous-209 vaccine, aim to prime and expand neoantigen-specific CD8+ T cells to selectively eliminate tumor cells while sparing healthy tissue (NCT04041310). Targeting these antigens offers a high degree of specificity and a reduced risk of central tolerance compared to traditional tumor-associated antigens.

Other names

AIM2 frameshift neoantigenAIM2-fsAIM2-FSPAbsent in melanoma 2 neoantigenAIM2 (A)10 frameshift peptide

Vaccine-induced activation of CD8+ and CD4+ T cells specific for the AIM2 frameshift neoantigen, leading to the targeted lysis of MSI-H tumor cells (PMID: 32690954).