
Tumor-Specific Antigens from Way Out There - nabla9
http://blogs.sciencemag.org/pipeline/archives/2018/12/11/tumor-specific-antigens-from-way-out-there
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dannykwells
This work is important but they were slightly beaten to the punch of the van
Allen group at Dana Farber in August:

[https://www.nature.com/articles/nbt.4239?WT.feed_name=subjec...](https://www.nature.com/articles/nbt.4239?WT.feed_name=subjects_antigen-
processing-and-presentation)

Also worth noting that vaccines using the exome-derived variant approach are
in the clinic and having good responses when combined with PD1:
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5577644/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5577644/)

Given this it will be interesting to see if these approaches are able to
improve beyond what's already working in diseases like melanoma, or
potentially move to low mutation burden tumors (pancreatic, gbm, etc.)

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jfarlow
I am curious how much of this is a bioinformatics insight. If your dataset is
looking under the lamp-post for coding sequences, then you'd be unlikely to
pull out non-coding regions for analysis. However, if you're strictly
empirical in your search for tumor-specific antigens, then such sequences
shouldn't be too much of a surprise. Either way, it's a very curious fact of
biology here.

On a separate note, the idea that unused viral sequences start showing up as
neo-antigens is also interesting. Those old viruses in our genome likely have
curious roles in other parts of our immune system such that a therapy
targeting them specifically might have odd repercussions.

Regardless, having more cancer-specific (cancer-enriched?) identifiers is a
good thing. And especially if used with synbio 'logic' like that found in bi-
Specific CARs or SynNotch, these just add more circles to the Venn-diagram
that is used to uniquely identify cancerous cells amongst our 'self'.

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dannykwells
Yeah, I think that's a reasonable point. There's definitely a good point of
lamp-post searching here, imo. The biggest challenge is that technologies like
mass spec can't get you a truly unbiased few of the tumor epi-nome, and so
it's hard to really get a truly measurement of what fraction are from where
(this is what they are trying to do here, but I think depth is still an
issue).

The viruses part is interesting too, but from a different angle: viral
specific t-cells are found, in abundance in tumors, and it's believed that
they aren't doing anything (i.e., they're bystanders) -
[https://www.ncbi.nlm.nih.gov/pubmed/29769722](https://www.ncbi.nlm.nih.gov/pubmed/29769722)

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ImaCake
I wonder if the immune system "leaves" some of these traditionally non-coding
sequences behind as a canary in the coal mine. If a cell starts undergoing
more frequent mutations on the road to becoming cancerous then a well placed
marker gene would be a great signal for the immune system to wake up and send
the cell into apotosis or to be phagocytosed.

