February 18, 2022 -- Applied DNA Sciences and EvviVax have published a manuscript detailing a preclinical study showing that LinearDNA vaccines used for cancer immunotherapy produced a strong immune and specific antitumoral response in preclinical mouse models. The study investigated the use of the LinearDNA platform to produce DNA vaccines targeting either tumor-associated antigens (TAAs) or tumor-specific antigens (TSAs, or tumor neoantigens).
The manuscript was published online on the bioRxiv preprint server and has been submitted for peer-reviewed publication. (bioRxiv, February 10, 2022).
LinearDNA is Applied DNA's proprietary, large-scale polymerase chain reaction-based manufacturing platform that allows for the large-scale production of specific DNA sequences.
DNA vaccines that target TAAs hold promise as potential pan-cancer vaccines that, when used in conjunction with existing standards of care, can increase the efficacy of cancer immunotherapies. DNA vaccines targeting TSAs, otherwise known as personalized cancer vaccines, also hold great promise in immunotherapy, as they can be customized to induce an immune response only against a patient's tumor, thereby limiting on-target, off-tumor effects.
One aspect of the study used a DNA vaccine targeting telomerase reverse transcriptase (TERT), a TAA that holds potential as a target for a pan-cancer vaccine. The TERT DNA vaccine was designed by EvviVax and exclusively licensed by Applied DNA Sciences for the LinearDNA platform for veterinary applications.
In prior clinical trials conducted by EvviVax, a plasmid form of the TERT DNA vaccine administered along with the standard of care chemotherapy was shown to increase the survival of canines with stage III/IV B-cell lymphoma from 37 weeks to 97 weeks.
For the study, the TERT DNA vaccine was administered to mice in either plasmid DNA or LinearDNA form and the immune response studied and compared. The study's results demonstrated that both the plasmid DNA and LinearDNA forms of the TERT DNA vaccine induced comparable immune responses in mouse models.
The second aspect of the study used a personalized DNA vaccine specifically targeting several TSAs expressed in a colon cancer mouse model. LinearDNA and plasmid DNA forms of the personalized cancer vaccine were administered to mice in the colon cancer model.
For both forms of the DNA vaccine, several cohorts also received immune checkpoint inhibitors (ICIs) based on anti-CTLA-4 and/or anti-PD1. The study demonstrated that the LinearDNA personalized vaccine produced an equal or greater immune and antitumoral response than the plasmid form of the same DNA vaccine, particularly when coupled with ICIs.