A neoantigen produced when an insertion or deletion shifts a gene's reading frame, generating a long stretch of entirely novel, highly foreign protein sequence.
Most neoantigens come from a single-letter change that swaps one amino acid for another — a small edit to an otherwise normal protein. A frameshift is more drastic. When an insertion or deletion adds or removes a number of DNA bases that is not a multiple of three, it shifts the reading frame, so every codon downstream is translated differently. The result is a long run of completely novel amino-acid sequence the body has never seen.
That makes frameshift neoantigens unusually immunogenic: they are more foreign than a typical point-mutation neoantigen, and a single frameshift can yield many candidate epitopes at once. They are especially abundant in tumors with mismatch-repair deficiency or microsatellite instability, which accumulate large numbers of insertions and deletions — and crucially, the same frameshift peptides recur across many such patients, making them shared neoantigens suitable for off-the-shelf vaccines.
This is the basis of cancer-interception vaccines like NOUS-209, which encodes frameshift neoantigens common to mismatch-repair-deficient tumors and is being tested to prevent cancer in people with Lynch syndrome.
It is a tumor neoantigen created when an insertion or deletion shifts a gene's reading frame, so all the downstream codons are read differently and the cell produces a long stretch of entirely novel protein sequence. That novel sequence is highly foreign to the immune system, which makes frameshift neoantigens strong vaccine targets.
Tumors with microsatellite instability or mismatch-repair deficiency cannot correct insertion/deletion errors during DNA replication, so they accumulate many small indels. A large share of those indels cause frameshifts, generating an abundance of frameshift neoantigens — and the same ones recur across patients, making them shared targets.