3 ms·
This seems so cool that I was immediately suspicious, but this isn't my area of expertise, so it's hard for me to understand the original paper: https://www.na
by rpdillon 1y ago
This seems so cool that I was immediately suspicious, but this isn't my area of expertise, so it's hard for me to understand the original paper:
https://www.nature.com/articles/s41551-025-01380-1 https://www.nature.com/articles/s41551-025-01380-1
This is the abstract, though, which suggests the need for a standard "in mice" disclaimer:
> The success of cancer immunotherapies is predicated on the targeting of highly expressed neoepitopes, which preferentially favours malignancies with high mutational burden. Here we show that early responses by type-I interferons mediate the success of immune checkpoint inhibitors as well as epitope spreading in poorly immunogenic tumours and that these interferon responses can be enhanced via systemic administration of lipid particles loaded with RNA coding for tumour-unspecific antigens. In mice, the immune responses of tumours sensitive to checkpoint inhibitors were transferable to resistant tumours and resulted in heightened immunity with antigenic spreading that protected the animals from tumour rechallenge. Our findings show that the resistance of tumours to immunotherapy is dictated by the absence of a damage response, which can be restored by boosting early type-I interferon responses to enable epitope spreading and self-amplifying responses in treatment-refractory tumours.
- _Microft 1y agoThe submitted article mentions that it was a study conducted on mice though? [0] "In this study on mice with melanoma, the vaccine was able to clear existing tumors that had proven drug-resistant."
- slater 1y agoIt's common for medical articles posted here to have a great-sounding breakthrough in their title, and you then have to read the article to find out it's only been done in mice. "en-mice'd/en-micing" is a term for mods editing titles, here :D
- asdff 1y agoLay people act like this is a trump card but this is just how science is done. You can't really perform this in humans without having some data that it may very well work. Mice have been pretty good models for cancer biology. Nature Biotechnology is also a good and selective journal.
- slater 1y agoI agree, I'm just mentioning it re: clickbait titles (not calling anyone out) vs. "oh, [xyz] hasn't been cured, there's just some promising results in mice"
- asdff 1y agoWell, the actual title is "Sensitization of tumours to immunotherapy by boosting early type-I interferon responses enables epitope spreading." This is just the reduced version for mass consumption. Keep in mind many people got a C in high school biology.
- CoastalCoder 1y agoOut of curiosity, are there examples of drug development that did poorly in animal models, but then did much better in human trials? I'm guessing this is rarely tested since animal modeling is usually a gating factor for human testing?
- mrosett 1y agoCheckpoint inhibitors (which are the primary driver of improved cancer treatment over the last 15 years and generate > $50B/year in sales) generally don't look very good preclinically. Even their clinical data can be hard to interpret prior to a large scale trial, which led to them almost being shelved. The catch here is that only two targets (PD(L)-1 and CTLA-4) turned out to work well in humans. All of the other immunotherapies that looked mediocre preclinically turned out to also be mediocre or entirely ineffective in humans.
- pasttense01 1y agoIf you ask: out of all the studies which have done well in mice what percent lead to successful drugs for humans: the answer is a very small percent.
- asdff 1y agoThis is the nature of research pipelines. If you ask: out of all the clinical trials that have shown promise in early human trials, what percent lead to successful drugs for humans: the answer is a very small percent.
- rolph 1y agoa bit of context: https://www.nature.com/articles/s41590-019-0416-z https://www.nature.com/articles/s41590-019-0416-z https://news.uthscsa.edu/scientists-create-first-mouse-model-with-complete-functional-human-immune-system/ https://news.uthscsa.edu/scientists-create-first-mouse-model... https://www.nature.com/articles/s41571-022-00721-2 https://www.nature.com/articles/s41571-022-00721-2 its not just, put it in a mouse, then guess about what happens to humans.
- karaterobot 1y agoThe linked article said the vaccine was still in pre-clinical trials, which means it hasn't been tested on humans yet. Mouse models are a stepping stone toward that. When you hear 'pre-clinical' think 'alpha testing', or 'proof of concept' stage.