Recent findings have positioned tumor mutation-derived neoepitopes as attractive targets for cancer immunotherapy. Cancer vaccines that deliver neoepitopes via various vaccine formulations have demonstrated promising preliminary results in patients and animal models. In the presented work, we assessed the ability of plasmid DNA to confer neoepitope immunogenicity and anti-tumor effect in two murine syngeneic cancer models. We demonstrated that neoepitope DNA vaccination led to anti-tumor immunity in the CT26 and B16F10 tumor models, with the long-lasting presence of neoepitope-specific T-cell responses in blood, spleen, and tumors after immunization. We further observed that engagement of both the CD4+ and CD8+ T cell compartments was essential to hamper tumor growth. Additionally, combination therapy with immune checkpoint inhibition provided an additive effect, superior to either monotherapy. DNA vaccination offers a versatile platform that allows the encoding of multiple neoepitopes in a single formulation and is thus a feasible strategy for personalized immunotherapy via neoepitope vaccination.
Tumor mutations giving rise to neoantigens have recently emerged as promising targets for cancer immunotherapy. Vaccines delivering tumor-specific neoantigens have demonstrated favorable efficacy and safety results in numerous preclinical and early clinical studies. However, selecting therapeutically relevant neoantigens amongst the myriad of cancer mutations has proven challenging. To overcome this, we have developed a proprietary AI-based target discovery platform, PIONEER, with enhanced predictive performance and increased precision. The PIONEER top-ranked neoantigens were selected and included in the personalized DNA vaccine candidate EVX-02. To assess the ability of the PIONEER designed neoantigen vaccine candidate to induce neoantigen immunogenicity and anti-tumor effect in preclinical models, mice were immunized with a mouse surrogate EVX-02 molecule, mEVX-02. mEVX-02 vaccination completely prevented establishment of tumors and induced neoantigen-specific, polyfunctional CD4+ and CD8+ T cells in the blood and spleen of immunized mice. An enhanced antitumor effect was obtained when combining mEVX-02 with anti-PD-1 mAb treatment. Encouraged by the preclinical results, we conducted a first-in-human multicenter Phase I clinical study of EVX-02 in combination with nivolumab in patients with resected malignant melanoma. The objectives of the trial were to investigate safety and tolerability, operational and clinical feasibility, and immunogenicity of the applied personal neoantigens. Each patient received a fully personalized drug that was produced in a complex process, from biopsy, through genome sequencing, AI-profiling, vaccine design, manufacturing, quality testing, and drug product release. This was succeeded with every single step for each patient. In all patients, EVX-02 treatment was well tolerated, and only very mild adverse events (AEs) have been observed in relation to immunization with EVX-02. Interim data demonstrated neoantigen-specific T-cell immune responses upon EVX-02 treatment and that the responses were mediated by activated CD4+ and CD8+ T cells. The measured T-cell responses were robust and long lasting. Together, these findings validate the precision and predictive power of our proprietary AI platform, PIONEER, and provide proof of mechanism for the DNA-delivery technology in that the encoded neoantigens gave rise to significant immune reactions. Citation Format: Daniela Kleine-Kohlbrecher, Nadia Viborg Petersen, Michail Angelos Pavlidis, Thomas Trolle, Stine Friis, Jens Kringelum, Anders Bundgaard Soerensen, Thomas Strandet Jepsen, Camilla Højgaard, Anders Jespersen, Erik D. Heegaard, Britt Winding Lauenborg, Birgitte Rønø. A personalized neoantigen vaccine is well tolerated and induces specific T-cell immune response in patients with resected melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB199.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2025 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.