Researchers from Stanford University have developed a vaccine capable of eliminating tumors in mice, with potentially no serious side effects. The treatment consists of injecting very small doses of two agents directly into the tumor, and works by activating the immune cells to target the cancer. Following the 97% success rate observed in mice, the first trial in human patients will begin later this year.
“We have a huge problem in cancer and we will never be satisfied until we find solutions for everyone,” said Dr. Ronald Levy, professor of oncology at Stanford University and senior author of the study.
The Field of Cancer Immunotherapy
While the T cells of our immune system are naturally able to recognize and destroy cancer cells, these can develop clever ways to keep the immune system at bay. For instance, they may modify their genetic expression to escape detection by T cells and go on to form tumors. As tumors grow, they may create a protective barrier that T-cells cannot penetrate. Some tumors can also deactivate T cells, and even turn T cells against each other.
Dr. Levy is one of the pioneers in the field of cancer immunotherapy, which aims at re-activating or enhancing the action of our immune system against cancer. Click here for a good overview of this interesting field of research.
Cancer immunotherapy can be highly effective. For example, CAR-T is an FDA-approved immunotherapy in which the patient’s own immune cells are collected and modified to fight cancer. Using this therapy raises the survival rate of pediatric patients that did not respond well to the first lines of treatment from 10-20% to 80%.
However, these treatments are often plagued with serious side effects and involve processes that are costly and laborious. The new vaccine has the advantage of being potentially cheaper and faster. The only expected side effects are soreness at the site of the injection and fever.
How Does It Work?
The treatment consists of injecting two agents directly into the tumor site. One agent is a short piece of DNA, called a CpG oligonucleotide. Working with nearby immune cells, it increases the expression of the receptor OX40 on the surface of T-cells. The second agent is an antibody against OX40. When the antibody binds to the receptor it activates the T-cells, which then target the cancer cells.
“When we use these two agents together, we see the elimination of tumors all over the body,” explained Levy. “This approach bypasses the need to identify tumor-specific immune targets and doesn’t require wholesale activation of the immune system or customization of a patient’s immune cells.”
Direct injection to the tumor site means the treatment activates only the T cells that already infiltrated the tumor. However, some of these activated T cells later leave the original tumor site and attack tumors at other locations.
Results in Mice
The research team used laboratory mice to test the effectiveness of the vaccine. They transplanted lymphoma cells to two different locations on the mice, and then injected the treatment into only one of the resulting tumors. The vaccine resulted in the regression not only of the first tumor, but also of the second.
Eighty seven out of 90 mice were completely cured after treatment. The three remaining mice experienced recurrence, but a second round of treatment led to regression again. The treatment was also successful in breast, colon, and melanoma cancers.
The new vaccine turned out to be very specific to each type of cancer. The scientists transplanted lymphoma cells from the same source in two different locations in the mice. They then transplanted colon cancer in a third location. After injecting one of the lymphoma tumors, the team observed a regression of both lymphoma tumors, but not of the colon cancer.
The study was published in January in the journal Science Translational Medicine.
Moving Forward
The two agents have already been shown to be safe for use in humans when used individually. But their safety when used together as a treatment for cancer is yet to be determined.
A Phase I clinical trial is set to begin later this year. Only a small number of patients will be enrolled in the study. For now, only patients with non-Hodgkin’s lymphoma will be able to participate.
In the future, doctors could administer the new vaccine to cancer patients before surgical removal of the tumor, in order to help destroy undetected metastases or even tumor recurrence.
“Getting the immune system to fight cancer is one of the most recent developments in cancer. People need to know that this is in its early days and we are still looking for safety and looking to make this as good as it can be,” said Dr. Levy.
If the FDA approves the new treatment, it is not expected to be available sooner than a year or two.