Stanford University researchers may have made a significant breakthrough in cancer research. Using a type of regenerative medicine known as induced pluripotent stem cells, also known as iPS cells or iPSCs, they have found a new way to attack – and possibly even prevent – tumor growth.
iPSCs, in their “pluripotency,” are developmentally immature cells that can be manipulated to become or “specialize in” nearly any cell or tissue found in the body. By becoming tumor cells, they can serve as a vaccine. iPSCs are well-established as effective for repairing trauma or disease damage but, for ethical reasons, only in animals. In a recent study, researchers sought to find out how they might benefit humans in the future.
iPSCs the New Anti-Cancer Vaccine?
What makes iPSCs interesting is their close resemblance to cancer cells. Like cancer cells, iPSCs also echo features of embryonic stem cells. These don’t yet have the growth restrictions seen in mature cells, so can multiply endlessly.
However, in order for iPSCs to work as a vaccine, they cannot multiply. Stanford University researchers hypothesized that injecting a cancer patient with their own iPSCs – genetically matched but radiated so unable to replicate – can safely expose the patient’s immune system to cancer without overwhelming it. This way, they can train the immune system to fight many types of tumor.
To test their theory, researchers explored iPS cells’ ability to form teratoma tumors, which contain many different cell types, in 4 groups of mice. The first group received injections of a control solution, the second genetically matched iPSCs, the third a generic adjuvant (an immune booster used alongside vaccines), and the final a combination of the iPSCs and adjuvant. After injecting each group once a week for 4 straight weeks, researchers transplanted individual mice with breast cancer, melanoma, and mesothelioma to see how they spread.
The results across all 3 cancer types were similar. All mice had developed tumors by the end of week 1, most robustly in the control groups. But in the fourth group, injected with the iPS-adjuvant combination, 7 out of 10 mice saw tumor regression. Two of the mice managed to completely reject the cancer cells and live for more than a year.
The Clinical Potential for Mesothelioma and Stem Cells
As researchers predicted, the iPSCs were able to provoke a system-wide, cancer-specific immune response. This is an especially exciting prospect for treatment of aggressive diseases like mesothelioma (a cancer caused exclusively by asbestos that forms on lung lining), which grows too rapidly for the immune system to target alone.
“This approach is particularly powerful because it allows us to expose the immune system to many different cancer-specific epitopes [the part of a cancer cell responsible for stimulating an immune response] simultaneously,” said Nigel Kooreman, MD, the study’s lead author. “Once activated, the immune system is on alert to target cancers as they develop throughout the body.”
In addition, Kooreman added, there appears to be no risk of inducing autoimmunity.
“What we saw in our vaccination studies is that these mice thrive over time, they grew, they gained weight and had healthy-looking fur … We have not seen any signs that it is not safe.”
Next on researchers’ agenda is human testing. Ideally, iPSCs could be used as part of standard adjuvant care after surgery, chemotherapy, radiation, or immunotherapy to prevent the regrowth of partially removed cancers. IPSC vaccines would follow several recent developments designed to stimulate the immune system to fight off cancer. But while many such immunotherapies boost the system in a non-specific way, few yet have the power to target specific types of cancer.
“Pending replication in humans, our findings indicate these cells may one day serve as a true patient-specific cancer vaccine,” said Joseph Wu, MD, PhD, the senior author. “Although much research remains to be done, the concept itself is pretty simple. We would take your blood, make iPSCs, and then inject the cells to prevent future cancers. I’m very excited about the future possibilities.”
