Evidence map›Paper›PMID 42565117›Full record

ReviewPrecision clinical medicine2026

Beyond the genetic code: orchestrating epigenetic and immune landscapes with multivalent mRNA-exosome vaccines.

Huiqin Bian, William Tse, Gang Huang, Shujun Liu

Abstract readReview
In one paragraph

Review in Precision clinical medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Huiqin BianDepartment of Medicine, The MetroHealth System, Case Western Reserve University, Cleveland, OH 44109, USA.
William TseDepartment of Medicine, The MetroHealth System, Case Western Reserve University, Cleveland, OH 44109, USA.
Gang HuangDepartment of Cell Systems & Anatomy Department of Pathology & Laboratory Medicine UT Health San Antonio, Joe R. and Teresa Lozano Long School of Medicine Mays Cancer Center at UT Health San Antonio, San Antonio, TX 78229, USA.ORCID https://orcid.org/0000-0002-5457-5358
Shujun LiuDepartment of Medicine, The MetroHealth System, Case Western Reserve University, Cleveland, OH 44109, USA.ORCID https://orcid.org/0000-0002-5347-8345

Funding

The Role of HIF1A-DNMT3A axis in AML1/ETO-Driven Acute MyelogenousLeukemiaR01CA248019 · NCI · UNIVERSITY OF MINNESOTA · PI LIU, SHUJUN · 2021 to 2025
$3.2M
Role of an Aberrant N6-Methyladenosine-LncRNA Axis in the Development and Maintenance of Drug Resistance through Regulating the Leukemia Stem CellR01CA266256 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI HUANG, GANG, LIU, SHUJUN · 2022 to 2025
$3.0M
NCI NIH HHS R01 CA248019NCI NIH HHS R01 CA266256
6 · The paper itself

Abstract

mRNA therapeutics are transitioning from transient anti-viral vaccines into precise cancer immunotherapies capable of orchestrating potent antigen-specific T-cell and humoral responses. However, therapeutic resistance within immunologically "cold" tumors remains a formidable barrier, necessitating multiaxial optimization across transcript architecture, neoantigen selection, delivery vector engineering, and tumor microenvironment (TME) reprogramming. This review synthesizes critical breakthroughs in mRNA biochemistry-including chemical nucleotide modifications, optimized untranslated regions, structural codon adjustments, and stringent purification methodologies-that extend transcript longevity while limiting off-target reactogenicity to maximize functional antigen expression. We evaluate multiomic neoantigen discovery workflows leveraging genomics, transcriptomics, immunoproteomics, and computational HLA-binding algorithms to refine patient-specific target selection. Next, we dissect advanced lipid nanoparticles, surface-functionalized biomaterials, and engineered extracellular vesicles optimized to enhance antigen-presenting cell tropism and lymphoid homing. We further detail how vaccine-induced cytokine fluxes actively remodel the TME, successfully reversing local immune tolerance and driving robust effector leukocyte infiltration into the tumor stroma. Specifically, we highlight the convergence of mRNA-mediated cytokine signaling and epigenetic imprinting, which cooperatively induce trained immunity for durable preventive surveillance. Finally, we delineate rational combinations with immune checkpoint blockades while addressing translational challenges: identifying predictive biomarkers, mapping presentation kinetics, and structuring adaptive clinical trial frameworks.

Indexed as

epigenetic reprogrammingexosome-mediated deliverymultivalent mRNA vaccinesprecision immunotherapytrained immunitytumor microenvironment plasticity

Identifiers

PMID42565117
PMCPMC13445983

What Socratic holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.