No, Im not talking about XMRV 😉
Im talking about using genetically modified viruses to treat prostate cancer 🙂
Broad antigenic coverage induced by vaccination with virus-based cDNA libraries cures established tumors
First, just to be clear, I dont know how this works. :-/
I mean, I know how this ‘works’, but I dont know how its actually working.
Firstly, it works nothing like the anti-tumor vaccines I have written about previously. In that case, scientists used HSV-1 as a Kamikaze– the virus delivers a protein to the cancer cell that attracted immune cells to kill the tumor.
Not how this prostate-cancer vaccine works.
They took tissue from a normal human prostate, and generated cDNA (you just want DNA versions of all the RNA the cells is making– not every cell is making all the same RNA/proteins). They then put that cDNA into Vesicular stomatitis viruses (VSV)– Every VSV had a different cDNA artificially inserted into its genome. So, when that virus goes on to infect a cell, it will make all the VSV proteins and it will make the little bit of normal prostate protein due to the cDNA in the viral DNA. The prostate proteins will then be presented in the infected cells MHC I molecules– ‘normal’ in an inappropriate context can generate an immune response… sooo… youre basically vaccinating against ‘prostate’.
The mice that got the anti-prostate vaccine lived longer/controlled tumors better than the PBS mice.
And this vaccine is not causing autoimmunity when it is injected intravenously. But it does induce autoimmunity if you inject the vaccine directly into the prostate.
I dont know how that works.
I mean, if they were doing this starting with a prostate tumor instead of a normal prostate, okay. But how the heck is a vaccine with a normal prostate clearing prostate tumors and not killing the normal prostate tissue??? And theyre doing this via a prostate-specific Th17 response (whiiiiich is usually indicative of autoimmunity) and CD4 T-cell response (think antibodies) instead of CD8 (cytotoxic T-cells) or Natural Killer cells, the cells who normally clear tumors.
I dont know how that works.
But 80% of the mice who got nine rounds of this vaccine cleared the tumor.
And then, they could make new vaccines from the tumors that were not cleared, and then some of the mice that couldnt totally clear the tumor with the generic vaccine, cleared it with a ‘personalized’ vaccine, and the ones who still got tumors, the vaccine ‘resistant’ tumors grew slower.
So, I am going to keep an eye on this, but I cant imagine a vaccination strategy like this is going to be in clinical trials, like, tomorrow. While under normal circumstances, I wouldnt need to know exactly how something was working before I believed it was working (eg the HPV vaccine kicks ass, but we still arent 100% how it is so effective), but in this case, I would need to know more about how this strategy is actually working before I would think it was safe enough for human clinical trials. I would be really, really concerned about autoimmunity. And they do not mention what they would use for human clinical trials anyway (they used human prostate cDNA in mice, which worked better than mouse prostate cDNA in mice— what would we use in humans? mouse prostate? chimpanzee? dog?).
Its cool, keep an eye on it, but temper this idea with a bit of ‘hmmm…’