124P - AI-designed cancer vaccines: Antigens from the dark genome are promising cancer vaccine targets

Background

Personalized cancer vaccines, targeting patients' tumor mutations, have significantly advanced cancer treatment. However, the use of neoantigens is restricted to tumors with sufficiently high mutational burden, limiting their use to selected cancer indications. The discovery of endogenous retroviruses (ERV) as relevant immunologic features contained in the dark genome and the research demonstrating their dynamic role in cancer development and progression provide potential prospects for therapeutic use. Evaxion Biotech’s core technology, AI-Immunology™ allows for identification and selection of ERVs as a new antigen source for designing personalized and precision therapeutic cancer vaccines. In the presented work we explore the efficacy of AI-Immunology™ identified ERVs as alternative antigens for cancer vaccines in preclinical mouse and human cell models. The basis of the tested vaccine designs are shared ERV antigenic hotspots, amino acid sequences containing one or more HLA allele ligands, targeting a broad population.

Methods

Mouse tumor studies were performed to validate AI-Immunology™ predicted murine ERV vaccine designs. For ERV antigen identification, RNA-sequencing data from different mouse tumor cell lines were used. The AI-Immunology™ selected antigens were encoded into plasmid DNA and mice were immunized intramuscularly with the plasmid DNA vaccine. The efficacy of the selected murine ERV antigens was evaluated based on the induction of functional antigen-specific T cells and ability to inhibit tumor growth. Furthermore, the ability of predicted human ERV antigens to induce an antigen-specific T-cell response was tested by in vitro stimulation of human PBMCs with ERV antigen peptides and measuring T-cell activation using ELISpot analysis.

Results

Immune analysis of the in vivo and in vitro studies demonstrate that the selected murine and human ERV antigenic hotspots induce significant antigen-specific T-cell responses in mice and human PBMCs. Murine ERV hotspots lead also to tumor growth inhibition in mice.

Conclusions

The obtained results prove that the AI-Immunology™ platform can identify functional and potent ERV antigenic hotspots. This warrants for further development towards clinical application.

Legal entity responsible for the study

Evaxion Biotech A/S.

Funding

Evaxion Biotech A/S.

Disclosure

D. Kleine-Kohlbrecher, S. Vester Kofoed, J. Kringelum, B. Rønø: Financial Interests, Personal, Full or part-time Employment: Evaxion Biotech; Financial Interests, Personal, Stocks/Shares: Evaxion Biotech. R. O. Andersen: Financial Interests, Personal, Full or part-time Employment: Evaxion Biotech A/S. M. B. Calvo, S. Friis, R. Villebro, M. S. Klausen, S.F. Thorsen: Financial Interests, Personal, Full or part-time Employment: Evaxion Biotech A/S; Financial Interests, Personal, Stocks/Shares: Evaxion Biotech A/S.