The iPSC-based cancer vaccine prevents tumor growth in pancreatic cancer (Published in 2020)

“Antitumor effects of iPSC-based cancer vaccine in pancreatic cancer”

The significance of this research
A research team at Stanford University has confirmed that induced pluripotent stem cell (iPSC)-based cancer vaccine prevents pancreatic cancer tumor growth in mice. The results of this study support further research into iPSC vaccination in pancreatic cancer.

Conventional Treatment for Pancreatic Cancer
Although surgery is the most effective treatment for pancreatic cancer, only about 10% of patients are diagnosed at a sufficiently early stage when surgical removal of the tumor is possible. The 5-year survival rate has remained in the single digits for the last several decades, although chemotherapy has also been available. Recently, immune checkpoint inhibitors have come to be used in the treatment of cancer. However, this therapy is less effective and difficult to treat pancreatic cancer, which has few genetic mutations, because it works better when the cancer has many genetic mutations.

Cancer Vaccine therapy
A vaccine is a type of medicine which can help boost the immune system. Vaccines are usually given to protect the body against infections. However, a cancer vaccine is used to boost the immune system to help it attack cancer cells. In cancer vaccine therapy, immune cells called T cells play a major role in attacking cancer cells. One T cell corresponds to one type of marker (antigen). To be able to recognize antigens, T cells need help from cells called antigen-presenting cells. When antigen-presenting cells are given an antigen that is specifically expressed in cancer, T cells that recognize the antigen proliferate and attack cancer cells. Since normal cells that do not have the antigen are not attacked, it is considered to be a safe treatment.

iPSC-based cancer vaccine therapy
In order for T cells to attack only cancer cells, it is necessary to find antigens that are present on cancer cells but not on normal cells. Recently, it has been found that the expression of genes shared by both iPSCs and cancer cells (iPSC-cancer signature genes) is upregulated. These genes are highly expressed in iPSCs and cancer cells, but only marginally or not at all in normal cells. Previous studies have reported that an iPSC-based cancer vaccine induces anti-tumor T cell immune responses in mice. However, it is unclear whether the vaccine also induces anti-tumor responses in tumors with low mutational burdens, such as pancreatic cancer.

Results of this study
The research team generated a mouse iPSC-based vaccine and tested its efficacy in a mouse model of pancreatic cancer to evaluate its anti-tumor effects. The iPSC vaccine consisted of iPSCs and an immune adjuvant that promotes antigen-presenting cell maturation. Mice were injected subcutaneously with (1) the combination of iPSCs + adjuvant, (2) iPSCs alone, (3) adjuvant alone, or (4) phosphate-buffered saline (PBS) control once a week for 4 weeks (n = 7–8/group), and then inoculated with pancreatic cancer cells. In the combination of iPSCs + adjuvant group, 75% of the vaccinated mice (6/8) completely rejected cancer cells. In mice vaccinated with iPSCs + adjuvant, the mean tumor volume was significantly lower than in mice treated with iPSCs (p = 0.0448), adjuvant (p < 0.0001) or PBS (p = 0.0050), by day 49 after tumor inoculation. These results demonstrated the effectiveness and the antitumor effects of the iPSC-based cancer vaccine in pancreatic cancer.

Additional information for researchers
The researchers confirmed that an iPSC-based cancer vaccine induces cytotoxic antitumor T cell and B cell immune responses in a mouse model of pancreatic ductal adenocarcinoma (PDAC). The cancer vaccine was also shown to reduce immunosuppressive Treg cells. They also found that shared gene expression profiles of “iPSC-cancer signature genes” are overexpressed in mouse and human iPSC lines, PDAC cells, and multiple human solid tumor types compared with normal tissues. These results support further studies of iPSC vaccination in PDAC and in other cancer types that have low mutational burdens.

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