A new class of drugs that combine artificial DNA structures with antibodies could make immunotherapies even more targeted—all you have to do is fold over and over again.
In a study published Aug. 17 in Nature Nanotechnology, researchers from the Ludwig Maximilian University of Munich, the Technical University of Munich and Helmholtz Munich described how agents dubbed programmable T-cell engagers, or PTEs, successfully activated T cells against cancer both in tumor cells and in mice.
The PTEs were developed using a method called DNA origami, where DNA strands are folded over and over again into nano-sized structures that can be mounted with payloads. (For all the DIYers out there, here’s a handy tutorial on how to make your own.) In this case, that payload is a set of four antibodies—two that bind to tumor cells on one side and two that attract T cells on the other. T cells destroy the cells that are marked with the antibodies.
“This approach permits us to produce all kinds of different PTEs and adapt them for optimized effects,” lead author Adrian Gottschlich, M.D., said in a press release. In theory, “infinite combinations are possible,” he added.
In this study, the team produced and tested out 105 of them, pitting them against human leukemia, prostate and breast cancer cell cultures containing T cells. Seeing that the PTEs could activate the T cells against the cancer cells—and reduce them more than 90% after 24 hours—they then moved to testing them in mice. First, they gave groups of five mice engrafted with leukemia cells each one of two types of PTEs targeting different antigens or a control solution.
Seeing more success with one of the PTEs, they tested it again to see whether it could control tumor growth over a longer period. This time, they monitored the mice for 21 days after injection. They found that the PTE reduced tumor growth in the treated mice compared to the untreated ones.
“In summary, our studies demonstrate the functionality of PTEs built from DNA origami … in vivo,” the researchers wrote in their paper.
Mounting different antibodies at the same time makes it so the PTEs can target multiple copies of the same antigen as well as sets of distinct antigens, making antigen recognition more precise, the scientists explained in the paper. This not only has the benefit of killing off more cancer cells while potentially minimizing T-cell exhaustion but also of better distinguishing between healthy cells and cancerous ones, they wrote.
Given their initial results, the team thinks it can develop a range of immunotherapy platforms from PTEs. Several of the scientists involved in the study have formed a startup, Plectonic Biotech, to develop and market the technology, according to the press release.
“We believe our results will enable the clinical application of DNA nanotechnologies and highlight the potential of DNA-origami-based biomolecular engineering strategies for medical applications,” the researchers wrote in the paper.