Tumor-Specific Antigens from Way Out There | Hacker News Reader

Tumor-Specific Antigens from Way Out There

blogs.sciencemag.org

31 pointsnabla94 comments

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...

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/

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.)

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'.

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

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.

Reply on news.ycombinator.com