In February, a team of researchers reported a completely different path for producing a vaccine that showed promise as both universal in its effect and as a true preventative inoculation, capable of warding off a variety of cancers even in mice that had never had cancer previously.4
The team theorized that, because of the similarities between embryonic cells and tumor cells, the body might be coaxed into an immunogenic anticancer response by introducing induced pluripotent stem (iPS) cells.
They used blood samples from the mice to create genetically matching iPS cells, irradiated the iPS cells to prevent proliferation and teratomas, and injected them into a group of mice once a week for 4 weeks. One group of mice received the iPS cells alone. Another received the cells plus the adjuvant CpG, a known immune-stimulating agent. A third group received CpG alone. Then they transplanted a mouse breast cancer line into the test animals. A fourth received a control solution.
The study’s senior author, Joseph C. Wu, MD, PhD, director of the Cardiovascular Institute and professor of medicine and radiology at the Stanford University School of Medicine in California, said all of the mice developed tumors at the injection site. But, while they grew robustly in the various control groups, they shrank in 7 of the 10 mice given the combination of iPS cells and CpG. Two completely rejected the tumor cells and lived cancer-free for more than a year after transplantation.
The authors found similar results in mice transplanted with melanoma and mesothelioma cell lines.
Remarkably, they found similar results when T cells from mice given the vaccine were injected into unvaccinated animals, “indicating that the iPS cell vaccine promotes an antigen-specific anti-tumor T cell response.”
The findings, Dr Wu said, raise 3 possibilities. The first: that someday researchers could create a vaccine from the blood of a patient with breast cancer, for example, and then inject them with the personalized iPS cells and adjuvant combination after the initial line of treatment has concluded. “Could it be possible,” he said, “that the woman mounts an immune response against her irradiated iPS cells, but then the repertoire of T cells would confer protection against future breast cancer recurrence?”
The second line of thought, he continued, is whether it’s possible to create an iPS cell vaccine from the blood of a high-risk person, say a 65-year-old smoker with a family history of cancer who may have a genome mutation, and immunize that person from future cancer formations.
“The third possibility is blue sky concept,” he said. “Just like we have vaccines for measles, mumps, rubella, chicken pox, hepatitis, and human papillomavirus, is it possible in the future to vaccinate a healthy person with his/her iPS cells to reduce the chance of cancer later in life?”
- Ott PA, Hu Z, Keskin DB, et al. An immunogenic personal neoantigen vaccine for patients with melanoma. Nature. 2017;547(7662):217-21. doi: 10.1038/nature22991
- Sahin U, Derhovanessian E, Miller M, et al. Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer. Nature. 2017;547(7662):222-6. doi: 10.1038/nature23003
- Kreiter S, Vormehr M, van de Roemer N, et al. Mutant MHC class II epitopes drive therapeutic immune responses to cancer. Nature. 2015;520(7549):692-6. doi: 10.1038/nature14426
- Kooreman NG, Kim Y, de Almeida PE, et al. Autologous iPSC-based vaccines elicit anti-tumor responses in vivo. Cell Stem Cell. 2018;22(4):501-13.e7. doi: 10.1016/j.stem.2018.01.016