RE: Inan . . .2 Feb 2019 16:08
lets look at it another way
average mutations on the cancer producing antigens results in about 1000's different epitopes ... of which only 1 or 2 may be useful ... even then its not that straight forward
its taken over 12 months to work on 3 ... with Scancell/Biontech deal ..
read this
It is conceivable that not all tumor-expressed neoantigens induce an autologous T cell response—for instance, because they are not efficiently cross presented. In addition, at least in preclinical models, there is evidence for immunodominance of tumor antigens, where the immune system becomes so fixated on particular antigens that it ignores other antigens that are both present and detectable in the tumor (29). If only a fraction of the available neoantigens would normally elicit T cell reactivity, the analyses carried out to date may underestimate the actual neoantigen repertoire. As a second consideration, it is important to realize that the formation of neoantigens is a probabilistic process in which each additional mutation increases the odds that a relevant neoantigen is created. Thus, in this “neoantigen lottery,” there will be cases in which despite a high mutational load, neoantigen-specific T cell reactivity is lacking or, vice versa, in which a tumor with only a handful of mutations will express an MHC class I– or class II–restricted neoantigen. Third, although we here make a prediction with regard to the frequency with which neoantigens that can potentially be recognized by the TCR repertoire are formed, it should be kept in mind that the presence of a neoantigen does not equal the induction of T cell reactivity. Human tumors vary substantially in the composition of their micro-environment, and this is likely to influence the ability of the T cell pool to respond to mutated antigens. Related to this, from a conceptual point of view, therapeutic manipulation of T cell reactivity would seem particularly attractive for tumor types that do express large numbers of antigens but in which the tumor microenvironment hinders the activation of the T cells that recognize them.
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