Tumor-specific frameshift peptide neoantigen

Tumor-specific frameshift peptide neoantigens are **novel peptides** generated from somatic frameshift mutations within the coding regions of genes in cancer cells. These mutations result in altered open reading frames that produce unique amino acid sequences—termed "neo-open reading frame" peptides—that are absent from normal human proteins. Because they arise exclusively from genetic alterations present only in tumor tissue and not in healthy cells, these peptides can be presented on major histocompatibility complex (MHC) molecules—primarily HLA class I—and recognized by CD8+ cytotoxic T lymphocytes[1]. This makes them highly attractive targets for personalized immunotherapy approaches such as therapeutic vaccines or adoptive cell transfer. Compared with missense mutation-derived antigens, each individual frameshift event can generate multiple novel epitopes due to the extended sequence change downstream of the mutation[1]. However, such events are less frequent than single amino acid substitutions but may offer higher specificity and immunogenicity due to their complete absence from the normal proteome[1].

Other names

Tumor-specific neoantigen (when specifically referring to those generated by frameshift mutations)Frameshift-derived neoantigenNeo-open reading frame (neoORF) peptide (context-dependent)

Recognition by T cell receptors on cytotoxic T lymphocytes following presentation on HLA class I molecules, leading to targeted immune-mediated killing of tumor cells expressing the neoantigens.