Researchers have known for some time that certain sequences of synthetic DNA induce potent immune responses when injected into animals and humans. A new study, conducted by Ying Tam, Ph.D., and colleagues at Inex Pharmaceuticals, demonstrates that encapsulating these synthetic DNAs in lipid-based nanoparticles greatly enhances the immunogenicity of these DNAs and that the nanoparticle-encased DNA sequences trigger antitumor activity when administered together with tumor-associated antigens.
Previous work by this group of investigators showed that lipid-based nanoparticles enhance the immune system stimulation activity of so-called CpG oligodeoxynucleotides by improving their uptake by immune cells. This boost occurs regardless of whether the nanoparticles are injected into the bloodstream, beneath the skin (subcutaneously), or directly into a tumor.
In the current study, the results of which were published in the journal Cancer Immunology and Immunotherapy, the investigators wanted to determine if the nanoparticle-encapsulated CpG construct could be used to create antitumor vaccines from tumor-associated antigens. To test this hypothesis, the researchers co-injected the nanoparticles and an antigen known as TRP-2, which is found on melanoma cells, into a mouse model of melanoma. Animals injected with TRP-2 or empty nanoparticles showed no antitumor response. In contrast, mice injected with CpG-containing nanoparticles and TRP-2 showed a large, statistically signficant decrease in the number of lung metastases.
This work is detailed in a paper titled, “Encapsulation in liposomal nanoparticles enhances the immunostimulatory, adjuvant and anti-tumor activity of subcutaneously administered CpG ODN.” Investigators from the University of British Columbia also participated in this study. An abstract of this paper is available through PubMed.