Abstract Cancers result from unique cellular transformation events resulting in the expression of cancer antigens that vary widely among different types of cancers. Ideally, a personalized cancer treatment approach needs to target specific cancer antigen. Efforts to induce specific immune responses against tumor associated antigens (TAAs) include the expression of TAAs through viral vectors capable of expressing multiple antigens. We have previously shown that the HSV-1(VC2) vaccine vector can induce potent antitumor immune responses utilizing the B16F10-derived syngeneic melanoma mouse model. To investigate whether heterologous antigens expressed by this vaccine vector could elicit potent immune responses, we generated the recombinant virus VC2-OVA that expresses the ovalbumin antigen (OVA) fused in-frame at the amino terminus of the viral VP26 protein. Western blot analysis of infected cells in cell culture showed efficient expression of the OVA-VP26 protein. The anti-tumor efficacy of the VC2-OVA virus was tested in the B16cOVA and E.G7-OVA mouse models that constitutively express the OVA antigen to test whether this vaccine can either prevent the formation of new tumors (prophylactic modality) or reduce tumor metastasis (therapeutic modality). In addition, we evaluated the differences between intradermal, subcutaneous, and intramuscular routes of vaccination with VC2-OVA. Treatment with VC2-OVA resulted in significant reduction of tumor formation and metastasis in both the prophylactic and therapeutic modalities. Importantly, the anti-tumor efficacy was dependent on the specific mouse tumor model. Further, we found that subcutaneous and intradermal was superior to intramuscular vaccination. The VC2 virus is available as a bacterial artificial chromosome allowing for the rapid isolation of recombinant VC2-derived virus expressing multiple tumor antigens. Therefore, these results demonstrate that the VC2 vaccine virus can be used to produce personalized cancer vaccines targeting specific TAAs. Citation Format: Ifeanyi K. Uche, Brent Stanfield, Jared Rudd, Konstantin Kousoulas, Paul J. Rider. Prospects for personalized cancer vaccines: The oncolytic and immunotherapeutic HSV-1(VC2) virus expressing an ovalbumin (OVA) antigen elicits robust anti-OVA immune responses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3570.