How does it work? 

Our body is largely made up of proteins, and those are encoded in the DNA, stored in each cell of the body. The DNA is read in triplets, in three letter words. The alphabet of DNA knows four letters, G, A, T and C. These can be combined into 64 triplet words. If one position is changed in the DNA this can lead to a change in the encoded protein. In this context we would call that a 'neoantigen'.  If, however, one or more letters are added or lost in the DNA, this can result in a shift in the combination of letters that form a triplet word.  

 A so called frame shift causes a track of nonsense to be expressed in a protein. 


Figure 1

In figure 1 & 2 every line is the protein sequence that occurs in the tumor of a patient whose DNA has been sequenced and where a frameshift has been observed (the actual mutation, insertion or deletion is in black). Only one of two possible frames shown here. These data were collected from a public database of tumors that have been sequenced (TCGA).

We discovered that particularly in genes whose function is to control the growth of cells there is a high level of frame shifts (this is because these frame shift mutations have inactivated the gene, contributing to the development of the tumor). Thus there are really large numbers of patients whose tumor have a frame shift in such a gene, and therefore express or can express antigens that are shared when compared with other patients. 

Conclusion: different frame shifts activate the same Frame



Figure 2

The shared property makes it possible to manufacture the vaccines against the Frames in advance, store them and supply them when a new patient is recognized as having that Frame in the tumor. 

A second advantage of the Frame neoantigens is that they are much more different from the original protein than 'traditional' neoantigens. There are many reasons in the literature to confirm that Frames are on average very antigenic, stand out like a foreign sequence, almost an invader such as a virus, and will thus most likely elicit a strong immune response. 

Also see the article in Nature.