This is certainly an interesting and theoretically promising method, that, if it works, should make it fairly easy to develop specific personalized "vaccines" for each person's cancer.
For background, dendritic cells are a type of antigen-presenting cells, which means their job is to pick up proteins, break them up into small pieces (antigens), and then show those pieces to T-cells, whereupon the T-cells can either say "looks like a self antigen, everything's fine" or say "that looks like a foreign antigen, raise the alarm!" and then initiate a specific immune response against that antigen.
The basic concept here is that if you have a specific protein that you want to raise an immune response against, you can do so by tricking dendritic cells into producing copies of that protein, which will then get presented along with all the other antigens for inspection by T-cells. You can pull off this trick by feeding RNA that encodes the target protein to the dendritic cells, and as a bonus, the fact that there's free RNA floating around triggers anti-viral defenses, which causes the T-cells to be extra suspicious of the antigens they're inspecting (i.e. it lowers their threshold for raising an immune response). But injecting RNA directly into your spleen isn't exactly practical, so instead they found that attaching the negatively charged RNA to some positively charged lipids in a specific ratio (which results in a specific ratio of charge to mass) causes them to localize to the spleen and then get taken up, translated, and presented by dendritic cells when injected intravenously.
So, put it all together, and the workflow for treating cancer looks something like this:
1. Find a protein produced by the cancer cells that is either sufficiently different from the same protein in normal cells (due to mutation) or not produced in normal cells.
2. Construct an RNA transcript that will produce that protein when translated.
3. Attach that RNA transcript to the liposomes in the appropriate ratio, and inject it into your bloodstream.
4. Let the immune system do its thing.
5. Repeat as necessary to keep the immune response active until it's killed all the cancer.
Obviously step 1 is still the hard part, and the paper chose as a proof of concept two example cancers for which this step was already done. But finding a viable cancer-specific antigen is certainly orders of magnitude easier than determining the mechanism of a cancer and then developing a treatment specific to that mechanism.
Yes, it certainly seems elegant, but with biology (and science in general), you always have to keep in mind that the (apparent) elegance of an approach is predicated on the assumption that we have an accurate understanding of how the system in question works, which frequently turns out not to be the case.
Thanks for the great summary. But I'm guessing previous immunotherapy based treatments are also based on stimulating T-cells to fight cancer cells. Any idea why they didn't work? This method only makes it easy to stimulate T-cells, but what about mutations in cancer.
The job of the immune system is to distinguish self from non-self and to seek and destroy any non-self that it discovers. If you want to get the immune system to fight something, you need to get it to recognize that something as non-self, preferably without also forcing it to recognize your own healthy cells as non-self (because then you'd have autoimmune disease). Cancer is an especially difficult case for the immune system because for the most part, cancer cells are your own cells with just a few mutations[1]. The vast majority of proteins produced by cancer cells are the same proteins that your healthy cells produce. They may be produced in different proportions, regulated differently, etc., but they are the same proteins. Even the proteins that mutated could have only a single amino acid change relative to the original. So the difference between healthy cells and cancer cells at a molecular level is much more subtle than the difference between your cells and bacterial cells, for example. It's not impossible for your immune system to identify cancer cells, but it's obviously not guaranteed either. (There's a nigh-untestable theory that a majority of cancers are actually detected and destroyed by the immune system long before they become symptomatic, so the ones we see are just the ones that managed to evade the immune system in their early stages.)
As I've mentioned above, this paper skips the hard part of finding a suitable protein target by picking two proof-of-concept cancer models for which a suitable "non-self" target is already known.
[1] Actually many mutations, but few that affect protein sequences, which are what T-cells mainly look at.
For background, dendritic cells are a type of antigen-presenting cells, which means their job is to pick up proteins, break them up into small pieces (antigens), and then show those pieces to T-cells, whereupon the T-cells can either say "looks like a self antigen, everything's fine" or say "that looks like a foreign antigen, raise the alarm!" and then initiate a specific immune response against that antigen.
The basic concept here is that if you have a specific protein that you want to raise an immune response against, you can do so by tricking dendritic cells into producing copies of that protein, which will then get presented along with all the other antigens for inspection by T-cells. You can pull off this trick by feeding RNA that encodes the target protein to the dendritic cells, and as a bonus, the fact that there's free RNA floating around triggers anti-viral defenses, which causes the T-cells to be extra suspicious of the antigens they're inspecting (i.e. it lowers their threshold for raising an immune response). But injecting RNA directly into your spleen isn't exactly practical, so instead they found that attaching the negatively charged RNA to some positively charged lipids in a specific ratio (which results in a specific ratio of charge to mass) causes them to localize to the spleen and then get taken up, translated, and presented by dendritic cells when injected intravenously.
So, put it all together, and the workflow for treating cancer looks something like this:
1. Find a protein produced by the cancer cells that is either sufficiently different from the same protein in normal cells (due to mutation) or not produced in normal cells.
2. Construct an RNA transcript that will produce that protein when translated.
3. Attach that RNA transcript to the liposomes in the appropriate ratio, and inject it into your bloodstream.
4. Let the immune system do its thing.
5. Repeat as necessary to keep the immune response active until it's killed all the cancer.
Obviously step 1 is still the hard part, and the paper chose as a proof of concept two example cancers for which this step was already done. But finding a viable cancer-specific antigen is certainly orders of magnitude easier than determining the mechanism of a cancer and then developing a treatment specific to that mechanism.