A vaccine made from inactivated pluripotent stem cells has been shown to stimulate a strong immune system response against breast, lung and skin cancers in mice, raising hopes that a human cancer vax could be just around the corner.
In a paper published in the journal Cell Stem Cell, a team led by Joseph Wu at Stanford University’s Cardiovascular Institute, US, reports the results of experiments conducted using “induced” pluripotent stem cells – that is, adult cells genetically reprogrammed to behave like embryonic cells.
The research involved administering different versions of the inactivated stem cell vaccine to mice, which were then variously also loaded up with breast cancer, mesothelioma and melanoma cells.
The results were encouraging. In the case of mice given breast cancer, within four weeks 70% of the mice were in full remission, and the remainder had significantly smaller tumours. Results in the skin and lung cancer cohorts were similar.
Using inactivated stem cells as a vaccine works because it facilitates an end-run around the ability of cancer cells to hide from host organism immune systems.
This, in itself, has been noted before. Indeed, a century ago, a researcher called Schone established that animals vaccinated with embryo tissues would reject transplanted tumours.
A decade ago, a couple of studies found that embryo cells and cancer cells shared a great number of RNA profiles and antigens, suggesting that the former could be used to prompt an immune response against tumours. However, because of ethical concerns, the strategy has never been tried on humans.
Induced pluripotent stem cells (iPSCs) can be used to create “whole cell” vaccines, in contrast to traditional vaccines which comprise inactivated organisms or protein products. The advantage of using whole cells is that all the antigens they harbour – including, crucially, any so far undiscovered by researchers – are passed on to the host.
This means that there are a larger number of foreign substances that can induce a response from the body’s T cells, the frontline of the immune system. Given the similarity between iPSC antigen loads and those of the cancer cells, there is thus a much greater chance that T cell reactions against the stem cells will also be effective against the tumours.
This chance is increased still further by the fact that a patient’s own cells can be used to create the iPSCs, ensuring that antigen loads are to all intents identical.
Wu and his colleagues conclude that their “data show the feasibility of creating broad tumour immunity against multiple cancer types using an iPSC-based vaccine that presents the immune system with large quantities of tumour antigens.”
The method, they add, could be used just a few weeks after initial diagnosis.
Commenting on the paper, Andrew Laslett of the Biomedical Manufacturing Program at CSIRO Manufacturing, in Australia, says that if the results in mice translated to humans then the “implications are potentially very significant”.