Although the human immune system is usually a concern for some gene-delivery systems — viral vector-based delivery methods, specifically — DNA-encoded plasmids may prove to be an exception. In theory, DNA-encoded plasmids should be able to avoid the inherent immunogenic problems associated with viral- and CRISPR-Cas9–based gene therapies because they are merely nucleic acid sequences and have no protein components involved during delivery to the target tissue. This is a critical distinction because the immune system can detect protein sequences very well and launch an immune response, whereas pure nucleic acid sequences can pass by largely undetected. In-human studies, however, will be needed before the immunogenicity of the DMAb platform can be known.
The DMAb technology has applications beyond generating monoclonal antibodies for the treatment of cancer. Dr Weiner and his colleagues are currently evaluating the DMAb platform across several diseases, and recently published preclinical studies on the platform’s utility in protecting against Ebola infection and treating high cholesterol.2,3
“There’s lot of interest in this technology,” Dr Weiner said. He said no clinical trials are planned to evaluate this technology for cancer or other diseases, but it is “likely” over the “next few years” someone will start to move this type of technology into the clinic.
Disclosure: The main study being highlighted was funded, in part, by Inovio Pharmaceuticals. For a full list of disclosures, please refer to the original study.
- Duperret EK, Trautz A, Stoltz R, et al. Synthetic DNA-encoded monoclonal antibody delivery of anti-CTLA-4 antibodies induces tumor shrinkage in vivo. Cancer Res. 2018;78(22):6363-6370.
- Patel A, Park DH, Davis CW, et al. In vivo delivery of synthetic human DNA-encoded monoclonal antibodies protect against ebolavirus infection in a mouse model. Cell Rep. 2018;25(7):1982-1993.
- Khoshnejad M, Patel A, Wojtak K, et al. Development of novel DNA-encoded PCSK9 monoclonal antibodies as lipid-lowering therapeutics [published online November 10, 2018]. Mol Ther. doi: 10.1016/j.ymthe.2018.10.016