OligoDOM: a T cell response enhancing platform applied to cancer immunotherapy

Judith Del Campo ¹ Séverine Valsesia ¹ Elsa Nikly ¹ Roberto Ruiu ² Antonella Iacoviello ² Elena Quaglino ² Federica Cavallo ² Dalil Hannani ³ Emilie Boucher ³ Florence Liliane Nicolas ¹ Alexandre Le Vert ¹ Francesco Doro ^1*

• ¹ OSIVAX, Lyon, France
• ² University of Turin, Turin, Piedmont, Italy
• ³ UMR5525 Techniques de l'Ingénierie Médicale et de la Complexité Informatique, Mathématiques et Applications, Grenoble (TIMC-IMAG), La Tronche, Rhône-Alpes, France

Background: Neoepitopes derived from tumors are attractive cancer immunotherapy targets, especially when combined with immune checkpoint inhibitors (CPIs). Vaccines using lipid nanoparticle (LNP)-encapsulated mRNA to deliver neoepitopes have shown encouraging results in patients and animal models, due to T cell-dependent responses. However, a low mutational burden is often a predictor of poor CPI response: the immune response against the few available mutations can be insufficient. An enhanced response to these few mutations could increase CPI efficacy. Here, we investigate the potential of OligoDOM™, a self-assembling sequence, to improve neoepitope immunogenicity and anti-tumor efficacy in murine cancer models.Methods: LNP-formulated mRNA constructs encoding short epitope strings fused with OligoDOM™ were tested. Immune responses in mice were compared between constructs with OligoDOM™ and their controls. Specific T cell responses against four tumor models (MC38, CT26, TC-1, B16-OVA) were measured using ELISpot in naïve mice. Two models (TC-1 and B16-OVA) were further selected for tumor growth efficacy testing.Results: LNP-formulated neoepitope-OligoDOM™ mRNA constructs induced a significantly superior immune response as compared to the control groups in 4 neoantigens tested. This increased specific immunogenicity is linked to anti-tumor growth effects in murine syngeneic cancer models such as the B16-OVA and TC-1. The induced T cell immune response significantly correlated with tumor growth rate reduction.Discussion: Combining OligoDOM™ and LNP-mRNA technologies offers a versatile platform that allows for efficient short neoepitope strings delivery. This approach represents a feasible, potentially effective strategy for personalized cancer immunotherapy.