Researchers have discovered an injectable “vaccine” that is delivered directly to mouse tumors to eliminate all traces of these tumors. Cancer researchers have found that the vaccine works in many different types of cancer, including the unprocessed metastasis in the same animal.
Scientists at the Stanford University, School of Medicine have developed potential treatments using two drugs that enhance the body’s immune system and are currently undergoing human clinical trials in patients with lymphoma. “When we used these two agents together, we saw systemic tumor clearance. This approach avoided the need to identify tumor-specific immune targets and did not require wholesale activation of the immune system or the customization of patient immune cells.”
Cancer immunotherapy is tricky. Because cancer cells are produced by the body, the immune system does not see the threat of intruders like viruses. This is why some cancer immunotherapy focuses on training the immune system to recognize cancer cells. This is an effective therapeutic field, but usually involves removing the patient’s immune cells from their bodies, genetically engineering them to attack the cancer, and injecting them, an expensive and time-consuming process.
Stanford vaccines can be cheaper and easier. It does not work like the vaccine you are familiar with. The researchers did not give prophylactic doses before infection but instead injected them directly into mice that already had tumors to one of the affected sites. “Our approach is to use a small amount of two drugs at once to stimulate immune cells. In mice, we have seen amazingly wide-ranging effects, including the elimination of tumors in animals.”
As the tumor grows, cells of the immune system, including T cells, recognize cancer cells as “aberrant proteins” and move. However, cancer cells can accumulate mutations to prevent the destruction of the immune system and suppress T cells that attack abnormal cells. The new vaccine works by reactivating these T cells. It combines two key agents. The first is a piece of DNA called a CpG oligonucleotide. This, together with other nearby immune cells, amplifies the expression of activated receptors on T cells called OX40, which is a member of the tumor necrosis factor receptor superfamily. The second agent is an antibody that binds to OX40, activating T cells to fight cancer cells. These two agents are injected directly into the tumor in microgram quantities. This means that they only activate the T cells in the tumor, and those cells that have already identified cancer cells are a threat. These cells begin to work on the tumor, but some T cells leave the tumor site to find and destroy other tumors in the body. To test it, experimental mice were transplanted with mouse lymphoma in two places, or genetically modified to develop breast cancer.
Of the 90 lymphoma-bearing mice, 87 were completely cured. The treatment was injected into one of the two tumors, both tumors were destroyed after injection.
The remaining 3 cases had lymphoma recurrence and were cleared after the second treatment. This treatment is also effective for mice genetically engineered to develop breast cancer. The researchers said that treating the first tumor usually increases the life span of the animal. The group then tested lymphoma and colon cancer mice and injected only lymphoma. Lymphoma is destroyed but colon cancer is not. This shows that the T cells in the tumor are specific to this tumor and therefore the treatment is not limited. But this means that immunotherapy is possible without genetic engineering cells in vitro.
The study was published in the journal Science.