As an Adjuvant Cancer Therapy, iPSC Vaccination Reactivated the Immune System

Pluripotent stem cells could support breast cancer, melanoma, and mesothelioma vaccines

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Researchers believe a patient-specific stem cell vaccine could become part of mesothelioma treatment and prevention.

The Stanford University School of Medicine recent study demonstrated a consistent immunologic response with genetically-altered stem cells in laboratory mice, which were carrying particular cancer cells.

Cancer cells and embryonic tissues share a number of cellular and molecular properties, suggesting that induced pluripotent stem cells (iPSCs) may be harnessed to elicit anti-tumor responses in cancer vaccines.

This study involved induced pluripotent stem cells (IPS), which are cells taken from the blood or skin and genetically reprogrammed.

This process enables cells to attack or prevent cancerous tumors when mixed with a generic immune-stimulating agent.

The iPS cells work as an anti-cancer vaccine because, like many cancer cells, they resemble developmentally immature progenitor cells, which are free from the growth restrictions built into mature cells that make up the body’s tissues.

Injecting iPS cells that genetically match the recipient, but that are unable to replicate, can safely expose the immune system to a variety of cancer-specific targets, the researchers found.

“We’ve learned that iPS cells are very similar on their surface to tumor cells,” said Joseph Wu, MD, Ph.D., director of Stanford’s Cardiovascular Institute.

“When we immunized an animal with genetically matching iPS cells, the immune system could be primed to reject the development of tumors in the future. Pending replication in humans, our findings indicate these cells may one day serve as a true patient-specific cancer vaccine,” said Dr. Wu.

To test this theory, these researchers used four groups of mice, infected separately with breast cancer, melanoma, and mesothelioma cells.

One was injected with a control solution, one received genetically matching iPS cells that had been irradiated to prevent the formation of teratomas, one received a generic immune-stimulating agent known as an adjuvant, and one received a combination of irradiated iPS cells and adjuvant.

The anti-tumor response rate was found to be similar in all three types of cancer.

As an adjuvant, the iPSC vaccine inhibited melanoma recurrence at the resection site and reduced metastatic tumor load, which was associated with fewer Th17 cells and increased CD11b+GR1hi myeloid cells.

Adoptive transfer of T cells isolated from vaccine-treated tumor-bearing mice inhibited tumor growth in unvaccinated recipients, indicating that the iPSC vaccine promotes an antigen-specific anti-tumor T cell response.

Our data suggest an easy, generalizable strategy for multiple types of cancer that could prove highly valuable in clinical immunotherapy.

The study is especially significant for mesothelioma, a rare cancer with no definitive cure and no FDA-approved second-line treatment options.

Researchers believe the next step will be testing their methods in a laboratory setting with human cancers and clinical trials.

“Although much research remains to be done, the concept itself is pretty simple,” Dr. Wu told the Stanford News Center.

“We would take your blood, make IPS cells and then inject the cells to prevent future cancers. I’m excited about future possibilities.”

Dr. Wu is the senior author of the study, which was published in Cell Stem Cell. Nigel Kooreman, MD, is the lead author. Dr. Wu is a member of Stanford Bio-X, the Stanford Cancer Institute, and the Stanford Child Health Research Institute. He is also the Simon H. Stertzer Professor.

Other Stanford authors of the study are postdoctoral scholars Youngkyun Kim, Ph.D., Ning-Yi Shao, MD, Ph.D., Tzu-Tang Wei, Ph.D., Hyoju Yi, Ph.D., and David Paik, Ph.D.; former postdoctoral scholars Patricia de Almeida, Ph.D., and Devaveena Dey, Ph.D.; medical resident Vittavat Termglinchan, MD; former research assistant Raman Nelakanti; former research associate Arnold Han, MD, Ph.D.; medical student Thomas Brouwer; instructor of medicine Idit Barfi, Ph.D.; professor of microbiology and immunology Mark Davis, Ph.D.; and professor of medicine Ronald Levy, MD.

No conflicts of interest were disclosed.

The research was supported by the National Institutes of Health (grants HL117756, HL113006, HL133272 and U19 AI057229), the California Institute for Regenerative Medicine and a Korean R&D grant. Stanford’s departments of Medicine and of Radiology also supported the work.