Safety, tolerability, and immunogenicity of WGc-043 in subjects with EBV-positive cancers: Results from an investigator-initiated trial.

139 Background: The Epstein-Barr virus (EBV) persists and spreads after infection in humans, leading to the occurrence and metastasis of a variety of cancers, posing great challenges in the treatment of cancer.. Conventional cancer therapies tend to have limited success and significant side effects. Therefore, there is an urgent need to develop more safe and efficient treatments such as innovative mRNA vaccines, which provide a new approach to cancer immunotherapy. WGc-043, an mRNA vaccine targeting EBV-positive tumor associated antigens, was evaluated for safety, tolerability, and immunogenicity in a prospective, single-center, investigator-initiated study. Methods: The study included 12 patients aged ≥18 with EBV-positive recurrent or metastatic nasopharyngeal carcinoma. Eligibility criteria included at least one measurable lesion, ECOG performance status 0-1, expected survival greater than three months, and no autoimmune disease. Participants were divided into three dose cohorts (25 μg, 50 μg, 100 μg) and received five administrations followed by optional continued monthly treatment of WGc-043 by intramuscular injection. The study assessed safety by adverse event monitoring, immune response based on the peripheral blood and tumor tissue sample analysis and efficacy according to imaging guidelines and irRECIST version 1.1. Results: The study results demonstrated that WGc-043 had a favorable safety profile with only grade 1 or 2 adverse events and fever (4/12) reported as the most common adverse event. Notably, two patients achieved partial response (PR) and five patients had stable disease (SD), highlighting the potential clinical efficacy of WGc-043. In addition, most (91.7%) subjects showed a significant reduction in plasma EBV DNA levels after administration. Immunogenicity analysis using IFN-γ ELISpot showed that 8 (66.7%) of the 12 enrolled patients developed strong specific immune responses against EBV-associated antigens, indicating that WGc-043 is a potent immunotherapy. Conclusions: This exploratory study underscores the safety and potential efficacy of WGc-043 as an mRNA vaccine for EBV-associated cancers, demonstrating its ability to induce specific immune responses and achieve substantial disease control in a challenging patient population, although further studies in larger clinical trials are needed. These results not only support the advancement of WGc-043 as a candidate for immunotherapy in EBV-positive cancers, but also highlight the translational potential of mRNA vaccine technology in the oncology landscape. Clinical trial information: NCT05714748 . [Table: see text]