805 ODI-2001, a personalized combinatorial immunotherapy shows antitumoral activity across different syngeneic mice tumor models, including 4T1

<h3>Background</h3> Immune checkpoint inhibitors’ (ICI) impressive effectiveness is dependent on pre-existing tumor-specific immune responses. ODI-2001 aims at inducing and strengthening pre-existing responses by combining a DNA vector expressing multiple neoepitopes, a live MVA vaccinia virus as a physiological adjuvant, and an anti-CTLA4 antibody as an amplifier of the immune priming. <h3>Methods</h3> ODI-2001 was subcutaneously administered in B16F10 melanoma and CT26 colon carcinoma tumor-bearing mice, or prior tumor cell inoculation in 4T1 breast cancer model. In B16F10, a combination of ODI-2001 with anti-PD1 was assessed. B16F10 and CT26 neoepitopes originate from the literature, while in 4T1 they were predicted using dedicated prediction algorithms (myNEO, Ghent, Belgium). Tumor volume and mouse survival were followed. Tumor infiltration by immune cells was analyzed by immunofluorescence. <h3>Results</h3> A significant improvement in survival was seen in mice treated with ODI-2001 in B16F10 mouse model, while adding anti-PD1 further improved survival. In B16F10-OVA-bearing mice, ODI-2001 increased tumor infiltration by immune cells. ODI-2001 significantly improved survival in mice bearing already established CT26 tumors. In 4T1 model, epitopes predicted using myNEO’s pipeline demonstrated an improved efficacy as compared to a set of neoepitopes extracted from the literature. Relapses in this spontaneously metastatic cell line appeared reduced in ODI-2001-treated mice, as well as the splenomegaly classically associated with tumor progression in this model. ODI-2001 induced no toxicity. <h3>Conclusions</h3> This data demonstrate the significant activity of ODI-2001 as an immunization platform across preclinical cancer models, both in monotherapy and combined with anti-PD1. ODI-2001 represents a promising option to enhance cancer-specific immune responses, potentially increasing the proportion of patients responding to immunotherapy treatments. Based on this data, a phase I with ODI-2001 in advanced solid tumors is under preparation. <h3>Ethics Approval</h3> All experiments performed minimized the number of animals using the adequate statistical method and their suffering. All experiments were approved by the local Ethics Committee and performed in a approved animal facility.