Induced pluripotent stem cells a potential cancer vaccine

Induced pluripotent stem cells, or iPS  cells, have been a hot topic in regenerative medicine since their discovery in 2006. They are produced directly from adult cells which have undergone a number of processes to return them to pluripotency, allowing them to re-differentiate and grow into any cell type, creating a single cell source that could be used to repair damaged tissues and organs.

Our findings indicate these cells may one day serve as a true patient-specific cancer vaccine” Dr Joseph Wu, senior study author

A new study from Stanford University, published in the journal Cell Stem Cell may have found another equally important use for iPS cells: priming the immune system to attack tumours. These findings could pave the way for personalised cancer vaccines that can either treat the cancer or prevent it from developing in the first place. The iPS cells have this potential anti-cancer ability due to their resemblance to developmentally immature progenitor cells, much like cancer cells. Injecting iPS cells derived from the patient themselves, meaning they would be genetically matched, and that are artificially unable to replicate can trigger a wide range of systemic immunological responses that target tumour-specific and -associated antigens.  

“We’ve learned that iPS cells are very similar on their surface to tumour cells. When we immunised an animal with genetically matching iPS cells, the immune system could be primed to reject the development of tumours in the future. Pending replication in humans, our findings indicate these cells may one day serve as a true patient-specific cancer vaccine.” said Joseph Wu, director of Stanford’s Cardiovascular Institute and senior study author.

iPS cells are made from cultured, isolated donor cells. Viral vectors are then used to transduce a combination of stem-cell associated genes, of which the 4 most studied are Oct3/4, Sox2, Klf4 and c-Myc, also called Yamanaka genes after the inventor of iPS cells. These genes encode transcription factors which allow for the ‘reprogramming’ of cells, altering transcriptional regulation of genes that produce embryonic stem (ES) cell specific proteins. These newly created proteins gradually revert the cell to pluripotency through many rounds of mitosis, creating something very similar to an ES cell. The cells are then tested for pluripotency by, for example, being injected into a mouse and observing for teratoma formation, a tumour which is made up of several different cell types.

As cancer cells mirror many features of iPS cells, most notably the ability to proliferate rapidly, Nigel Kooreman, the lead author, and Joseph Wu decided to compare gene expression panels of the two cell types. They found that they shared many similarities, most importantly several shared epitopes, the part of the antigen that is recognised by the immune system. They can trigger an immune response, generating immunity that would destroy any cell that possesses that epitope if it were to be found in the body in the future.

To test this theory, 4 groups of mice were investigated: A control group; a group that received genetically matching iPS cells, irradiated to prevent teratoma formation; a group that received a generic adjuvant, a substance that increases the body’s immune response; and a group that received irradiated iPS cells with the adjuvant. After 4 injections spread over a one month period, breast cancer cells were transplanted into the mice to examine tumour growth. A week later, all mice had developed tumours, however in the iPS cell + adjuvant group, tumour growth had been slower, with two of the mice able to completely prevent tumour proliferation.

 

 

Once activated, the immune system is on alert to target cancers as they develop throughout the body”

Nigel Kooreman, former postdoctoral researcher and lead author

Kooreman and colleagues went on to discover that T cells from vaccinated mice could be isolated and injected into unvaccinated mice to treat the tumour. Furthermore, the growth of teratomas was significantly reduced when the T cells were injected into mice treated with non-irradiated iPS cells, demonstrating that the T cells can recognise epitopes from both the cancer cells and iPS cells.  

“This approach is particularly powerful because it allows us to expose the immune system to many different cancer-specific epitopes simultaneously. Once activated, the immune system is on alert to target cancers as they develop throughout the body” said Kooreman.

The authors believe their findings could be used to create broad tumour immunity against multiple types of cancer by using iPS cell based vaccines, presenting the immune system with many different tumour epitopes at the same time.

“Although much research remains to be done, the concept itself is pretty simple. We would take your blood, make iPS cells and then inject the cells to prevent future cancers. I’m very excited about the future possibilities” states Wu.