Researchers from the São Paulo State Cancer Institute (ICESP) with their new findings injected a biomedical engineered virus in mice with prostate cancer to fight back the tumor cells. In some of the cases, the modified virus itself made the tumor cells more vulnerable to chemotherapy drugs stopping the tumor progression.
The findings of the research paper “Combination of cabazitaxel and p53 gene therapy abolishes prostate carcinoma tumor growth” are published in the journal the Nature.
The research was led by Bryan Eric Strauss who explains the research by saying, “We used a combination of gene therapy and chemotherapy to combat prostate cancer in mice. We chose the weapon we considered most likely to work as a tumor suppressant.”
They made use of the p53 gene that is known for controlling cell death in both rodents and humans. P53 was inserted in adenovirus which was then administered to the tumors in the mice.
Strauss explains, “First, we implanted human prostate cancer cells in the mice and waited for tumors to grow. We then injected the virus directly into the tumors. We repeated this procedure several times. On two of these occasions, we also systemically administered cabazitaxel, a drug commonly used in chemotherapy. After that, we observed the mice see if the tumors developed.”
All the mice had tumor cells of prostate cancer. For a control group, researchers added another virus in the mice. The second group received a virus having p53 while the third received only the drug cabazitaxel. In the fourth one, a combination of both the virus and drug was injected in the mice.
The modified virus actually gains access to the genetic material of the nucleus triggering cell death. The p53 gene proved successful in killing the tumor cells of prostate cancer.
He says, “Individual treatments with p53 or cabazitaxel alone had an intermediate effect in terms of controlling tumor growth, but the combination had the most striking result, totally inhibiting tumors,”
It was clear in the experiment that it is due to the modified virus. He further said, “The association of the drug with gene therapy resulted in full control of tumor growth. In other words, we observed an additive or even synergistic effect. It can also be assumed that the virus with p53 made tumor cells more sensitive to the action of the chemotherapy drug.”
Strauss asserts that the virus needs to be injected directly into the tumor cells and not in the bloodstream. Chemotherapy causes leukopenia (loss of white blood cells). Strauss says, “In our study, we used a subtherapeutic dose, which was not sufficient to control the tumor. This was done to avoid leukopenia.”
It is necessary to stimulate the person’s immune system as the p53 gene does not guarantee the complete elimination of the tumor cells. If the combination of p53 and cabazitaxel is insufficient for this purpose, Strauss asks for using additional gene like an interferon-beta gene.
“Both p53 and interferon-beta can kill tumor cells. We wanted to combine them for cell death to wake up the immune system. This is known as immunogenic cell death,” he says.
This idea is based on the findings of previous researches which shows that the combination can stimulate the immune system to stop recognizing the tumor cells as a part of their own body and start considering it as a foreign agent.
“When this happens, the immune system combats tumor cells both at the treatment site and in tumors located elsewhere.” Strauss concludes by saying, “Our goal now is to refine these approaches. We’re engaged in experiments to find out whether they deserve to advance to the stage of clinical trials in human patients.”