Abstract 5842: A novel formulated neoantigen DNA vaccine with promising anticancer efficacy in B16F10 mouse melanoma model

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Abstract Cancer vaccine approaches targeting neoantigens are gaining credence due to their specificity for tumors while sparing healthy tissues. Cancer vaccines based on DNA technology are attractive anti-cancer therapeutic tools due to their ability to elicit an effector T-cell-based immune responses. We report the development of a novel DNA-based cancer vaccine that relies on the delivery of a plasmid DNA vector encompassing immune epitopes of multiple neoantigens delivered with a novel synthetic DNA delivery system with the aim to elicit a broader immune response against cancer. The formulated vaccine was also investigated in combination with different adjuvants to maximize the anti-cancer responses. The vaccine vector encoding the immunogenic epitopes of multiple melanoma neoantigens and flanked by signal peptide at N-terminus and an MHC-targeted domain at the C-terminus end was formulated with a functionalized novel synthetic polymer with or without the adjuvants Poly I:C, diABZI, a STING agonist, or a mouse IL-12 plasmid. Mice were implanted subcutaneously with 0.5 x 106 B16F10 tumor cells on Day 0 and vaccinated intramuscularly with the DNA formulations on Day 2, 9, 16 and 23, and monitored for tumor growth and survival . For cellular responses, mice were injected intramuscularly with the DNA formulations on Day 0, 21, 42 and sacrificed 7 days later for cellular immune response by ELISPOT assay. Vaccination with formulated DNA alone yielded a significant inhibition (60%, p<0.01) of tumor growth and improved survival. Addition of Poly I:C, diABZI, or IL-12 plasmid further augmented the tumor inhibition to 90%(p<0.0001), 94%(p<0.0001), and 88% (p<0.0001), respectively, and improved the survival outcome. All animals in the adjuvant groups also lived longer. The anti-tumor efficacy results are supported by the onset of robust T-cell responses in all treatment groups supporting the involvement of immune activation in the action of this novel DNA vaccine that does not require a virus or device and can be manufactured rapidly with a simple and cost-effective manufacturing process critical for the viability of cancer vaccines. Citation Format: Kempaiah Rayavara, Subeena Sood, Majed Matar, Jessica Kim, John Henderson, Jeff Sparks, Meredyth Kinsella, Olivia Signer, Joseph Rogers, Chelsey Bellmon, Khursheed Anwer. A novel formulated neoantigen DNA vaccine with promising anticancer efficacy in B16F10 mouse melanoma model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5842.

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