National University of Singapore
NOVEL RNA-BASED CANCER VACCINE FOR AML IMMUNOTHERAPY
Abstract
dc:description.abstractAcute Myeloid Leukemia is a rapidly progressing malignancy. We hypothesize that personalized mRNA cancer vaccine can be a viable treatment strategy for AML patients. Using mouse AML cell lines, we have found candidate neoepitopes within intron polyadenylation sites, retained-intron sites, and somatic mutation sites. Screen for immunogenic neoepitopes using 102 synthetic peptides was performed in ELISpot assays. Our final 10 candidates were cloned into a vaccine construct. mRNA cancer vaccines were synthesized using our optimized laboratory-scale synthesis pipeline. Using manganese lipid nanoparticles as a delivery agent, the treatment vaccine has successfully rid one mouse of this aggressive leukemia. Flow cytometry analysis has confirmed a decrease in leukemic burden in both the liver and lung. Memory T cells play a key role in this. Combination therapy with anti-programmed death-ligand 1 has provided the AML mice with significant survival benefits. These data provide preclinical evidence for human study in the future.
Author and committee
dc:creator, dc:contributor.*- Author dc:creator
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- THAM GUO HONG