{"id":{"repo_id":"nus","oai_identifier":"oai:scholarbank.nus.edu.sg:10635/249554"},"canonical_url":"https://search.dev.ndltd.org/etd/nus/oai:scholarbank.nus.edu.sg:10635/249554","repository":{"repo_id":"nus","name":"National University of Singapore","base_url":"https://scholarbank.nus.edu.sg/oai/request"},"display":{"title":"NOVEL RNA-BASED CANCER VACCINE FOR AML IMMUNOTHERAPY","abstract":"Acute 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.","abstract_html":"Acute 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.","abstract_has_math":false,"creators":["THAM GUO HONG"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2024,"date_issued":"2024-01-26","date_published":"2024-01-26","updated_at":"2026-07-24T03:32:43Z","subjects":["C1498 cell line","anti-PD-L1","Neoantigens","Immunotherapy","mRNA Cancer Vaccines","Acute Myeloid Leukemia"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":null,"outbound_label":null,"outbound_source":null},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["THAM GUO HONG"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.issued","label":"Date","values":["2024-01-26"]},{"key":"dc:relation.isreferencedby","label":"Dc Relation Isreferencedby","values":["https://scholarbank.nus.edu.sg/handle/10635/249554"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["C1498 cell line","anti-PD-L1","Neoantigens","Immunotherapy","mRNA Cancer Vaccines","Acute Myeloid Leukemia"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://scholarbank.nus.edu.sg/bitstreams/05f2bc39-3266-4118-8c32-54a83bb02ed2/download"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Acute 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. 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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. 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