Personalized mRNA cancer vaccine for AML immunotherapy 4133

Abstract Description Acute Myeloid Leukemia (AML) is a rapidly progressing malignancy relying primarily on chemotherapy as the frontline treatment option. We hypothesize that personalized mRNA cancer vaccine can be a viable treatment strategy for AML patients. Next generation sequencing was performed and three different neoepitope prediction pipelines were utilized to identify potential immunogenic neoepitopes. Candidate neoepitopes within intron polyadenylation sites, retained intron sites and somatic mutation sites were found. With these candidates, we screened for immunogenic epitopes using a total of 102 synthetic peptides ELISpot assays. 10 candidates were cloned into a vaccine construct. mRNA cancer vaccines were synthesized using our optimized laboratory-scale mRNA synthesis pipeline. With manganese lipid nanoparticles as a delivery agent, we observed a trend of prolonged survival in AML mouse model with the vaccine treatment. Flow cytometry analysis has confirmed the effectiveness of the treatment vaccine with decreased leukemic burden in both liver and lung. The percentages of memory T cells are significantly higher in mice with the vaccine treatment. Combination therapy with anti-PD-L1 mRNA has provided statistically significant survival benefits in AML mice. We have provided preclinical results for potential translation into human study. Neoepitope screening platform has also been established to validate the prediction pipelines in AML patients. Funding Sources Supported by NMRC CIRG MOH-000945 Topic Categories Vaccines and Immunotherapy (VAC)