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Multiple patient-specific tumor targets

Molecular classification
Neoantigen, Tumor-specific antigen, Peptide-MHC complex
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Overview

Multiple patient-specific tumor targets refers to a personalized therapeutic strategy where a unique set of antigens, primarily neoantigens, is identified for an individual patient's malignancy (Schumacher & Schreiber, 2015). These targets arise from somatic mutations—such as point mutations, insertions, or deletions—that are present only in tumor cells and not in normal tissues (Blass & Ott, 2021). By targeting these specific mutations, therapies can achieve high precision and minimize off-target effects on healthy cells (NCI, 2023). The process typically involves whole-exome sequencing of the tumor and healthy tissue to identify non-synonymous mutations, followed by bioinformatic prediction of which mutated peptides will best bind to the patient's specific HLA molecules (Sahin & Türeci, 2018). These predicted neoantigens are then incorporated into various platforms, including mRNA, DNA, or peptide vaccines, to stimulate a robust T-cell mediated immune response (Ott et al., 2017). This approach is central to the development of precision oncology, allowing for the creation of tailored therapies based on the genetic profile of a single patient's cancer. Clinical applications are currently focused on high-mutation-burden tumors, where the likelihood of identifying immunogenic neoantigens is highest. This approach is currently being evaluated in numerous clinical trials for cancers such as melanoma, non-small cell lung cancer, and pancreatic cancer (ClinicalTrials.gov, 2024).

Other names
NeoantigensPersonalized tumor antigensTumor-specific neoantigensPatient-specific neoepitopesTSAs
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Mechanism of action

Vaccine-mediated delivery of patient-specific neoepitopes (as mRNA, DNA, or peptides) to antigen-presenting cells, which then present these antigens to T cells, triggering a targeted cytotoxic immune response against tumor cells expressing those specific mutations (Sahin & Türeci, 2018).

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Biological functions

Immune responseAntigen presentationT-cell activation
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Disease associations

Cancer
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Safety considerations

Manufacturing complexity and high costTime-to-treatment delays due to production requirementsPotential for immune-related adverse events (irAEs)Tumor immune escape via antigen loss or MHC downregulation
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Interacting drugs

mRNA-4157 (V940)

4 more in the full profile.

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Biomarkers

Tumor Mutational Burden (TMB)HLA-A/B/C typingNeoantigen loadT-cell receptor (TCR) clonality

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