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

Area of Science:

• Immunology
• Oncology
• Biotechnology

Background:

• Neoepitopes are key targets for cancer immunotherapy, particularly when combined with immune checkpoint inhibitors (CPIs).
• Lipid nanoparticle (LNP)-encapsulated mRNA vaccines show promise for delivering neoepitopes and eliciting T cell responses.
• Low tumor mutational burden can limit CPI efficacy due to insufficient immune responses against available neoepitopes.

Purpose of the Study:

• To investigate the potential of oligoDOM™, a self-assembling sequence, to enhance neoepitope immunogenicity.
• To evaluate the impact of oligoDOM™ on antitumor efficacy in murine cancer models.
• To assess the feasibility of combining oligoDOM™ with LNP-mRNA technology for personalized cancer immunotherapy.

Main Methods:

• LNP-formulated mRNA constructs encoding short epitope strings fused with oligoDOM™ were developed and tested.
• Specific T-cell responses against four tumor models (MC38, CT26, TC-1, B16-OVA) were measured using ELISpot assays in naïve mice.
• Tumor growth efficacy was assessed in TC-1 and B16-OVA models.

Main Results:

• LNP-formulated neoepitope-oligoDOM™ mRNA constructs induced significantly superior immune responses compared to control groups across four neoantigens.
• This enhanced immunogenicity correlated with significant antitumor effects in murine syngeneic cancer models (B16-OVA and TC-1).
• The magnitude of the induced T-cell immune response was directly linked to the reduction in tumor growth rate.

Conclusions:

• The combination of oligoDOM™ and LNP-mRNA technology provides a versatile platform for efficient delivery of short neoepitope strings.
• This approach represents a feasible and potentially effective strategy for developing personalized cancer immunotherapies.
• Enhancing immune responses to limited neoepitopes can improve the efficacy of cancer treatments, including CPIs.