Stanford Medicine (SM) are doubling-down on their work on so-called “cancer vaccines” – treatments that induce the body’s own immune system to annihilate cancerous cells. Following on from another slightly different vaccine study published earlier this month, this paper describes how stem cells have been used in mice to not just shrink tumors, but in some cases immunize their bodies against future reintroductions of the cancer.
This new work, published in Cell: Stem Cell, relies on the use of induced pluripotent stem cells, or iPSCs. These little wonders are derived from skin or blood cells that have been chemically reprogrammed to return to this primitive state. Given a little technical prodding, they can transform into any type of cell that’s required.
You can see why, given this ability, they’re being considered to game-changers in the world of regenerative, organ-growing research. An SM-led team wondered how they may fair when it comes to treating cancer, so they set to work.
Cancer cells are often left unchecked by immune systems. Despite their abnormalities, they are still our own cells, so they don’t register as foreign invaders. This camouflage means that even if they are identified as a threat, it’s often too late to stop it as their proliferation has spiraled out of control. Immunotherapy hopes to overcome this identification problem.
To wit, the team noticed that the gene expressions – the “on-off” state of a gene or series of genes – of cancer cells and iPSCs were fairly comparable, at least in mice. This suggested that both posses similar proteins on their surfaces, and it was suspected that because of this, the team could use the IPSCs as a warning shot: a passive blueprint that would tell the immune system what exactly it should be seeking to destroy.
In order to confirm the validity of this hypothesis, they injected tumor-bearing mice with genetically-identical IPSCs, irradiated to ensure they didn’t grow uncontrollably into tumors themselves. In some cases, they were also accompanied by an additional immune-stimulating agent.
It worked: given an injection of the IPSCs and the agent once a week for four weeks, the mice’s immune system registered the IPSC surface proteins, and subsequently destroyed the matching cancer cells. Out of 10 breast cancer-riddled mice in this vaccinated group, the tumors shrank in size in seven of them, and two were able to “fully reject” new cancer cells even after they were reintroduced to them a year later, according to the study – evidence of a cancer prevention mechanism at play.
The vaccine also appears to work somewhat effectively on both skin cancer and a particularly difficult-to-treat type named mesothelioma. Each time, the IPSCs had the potential to grow into that specific cancer type, but were irradiated to prevent them from doing so – and in turn, this provided the immune system with a safe way to identify the real threat.
Although the study describes this work as being in the “proof of concept” stage, the potential for this treatment is obvious. If this vaccine could be applied to humans, it may not only shrink or destroy tumors, but prevent future ones from arising, all using cells from the patient’s own body.
"We propose that immunotherapy - and especially our vaccine - be used in conjunction with established therapies," senior author Prof. Joseph Wu, MD, PhD, director of Stanford's Cardiovascular Institute, told IFLScience.
"Further development of immunotherapies with increased specificity to the cancer without (or with limited) adverse effects will hopefully one day limit the use of systemic therapies with significant side effects."
Aimee Eckert, a doctoral researcher focusing on cancer biology at the University of Sussex – and who wasn’t involved in the study – tells IFLScience this is a “promising step,” but at this stage its likeliness to work in a human patient is uncertain.
The study notes risks of an immune system overreaction, as well as the danger of immune cells hidden with the cores of tumors “which are indoctrinated by the cancer cells to be less reactive against other cancer cells.”
So far, the work has only been conducted on mice – a useful but imperfect proxy to people. “They are going to test it on human tissue in a laboratory-based setting next, though, which is exciting,” Eckert noted.