In one of the most common forms of cancer immunotherapy, scientists inject foreign substances into the body to elicit immune responses at tumor sites. Unfortunately, this type of immunotherapy has only generated limited results in the past. On top of this obstacle, there are also a number of side effects to immunotherapy. Among the many strides that are being made in cancer research and treatment, a solution to these downsides to immunotherapy may be on the way. An NIH team is trying to rectify the issues by testing a nanovaccine in mice. This may make cancer immunotherapy more effective and even reduce the side effects.
Scientists at the National Institute of Biomedical Imaging and Bioengineering used the injection of unmethylated cytosine-guanine oligodeoxynucleotides (CpG), a substance that occurs in bacteria but rarely in mammals, as the basis for their development of the nanovaccine. CpG stimulates the immune response when it is injected into a tumor, but because of its molecules’ negative charge and small size, it doesn’t stay in the tumor for a long time.
The team at the NIBIB is working on a solution to this problem. They have created a vaccine that packages CpG in a way that prevents the body from clearing it so rapidly. The vaccine combines CpG DNA with an inorganic compound called magnesium pyrophosphate, creating tiny flowerlike complexes that immune cells take up. This is why the vaccine is dubbed a DNA-inorganic hybrid nanovaccine. In addition to preventing the CpG molecules from degrading, the packaging has another important ability. It can be manipulated in size so that is will not be eliminated from the body as quickly.
By adding fluorescent molecules into the process, the team was able to display that the nanovaccine was efficiently taken by two different immune cells in the mice. The scientists then observed how the nanovaccine stacked up against regular CpG molecules in mice that were given melanoma. Each treatment was given in two doses which were 6 days apart. The nanovaccine was able to inhibit tumor growth to a greater extent than the CpG molecules did, and it also remained in the tumor for a longer period of time than the CpG molecules.
The researchers also demonstrated how the nanovaccine reduce side effects of immunotherapy. The side effect that they focused on in order to demonstrate this was an enlarged spleen. The mice treated with the regular CpGs had spleens weighing double the weight of the spleens in the mice who were treated with the nanovaccine.
With its enhanced ability to inhibit tumor growth, to stay inside the tumor, and to reduce side effects, this hybrid nanovaccine has the potential make a big difference in cancer immunotherapy.
In the future, the scientists intend to combine the nanovaccine with antigens that are specific to certain tumors. They hope this will help the nanovaccine to specifically target cancerous cells. They also have an interest in using the nanovaccine in a combination therapy with radiation therapy and chemotherapy. This is just the beginning of the journey toward more effective immunotherapy with less severe side effects. There are still many more steps to take in this exciting and revolutionary endeavor.