Target intelligence / Profile preview

Patient-specific tumor neoantigen peptides presented on Major Histocompatibility Complex (MHC) molecules (NeoAg-MHC)

Target
NeoAg-MHC
Molecular classification
Antigen, Peptide-MHC complex
01

Overview

Patient-specific tumor neoantigen peptides presented on Major Histocompatibility Complex (MHC) molecules are highly specific targets for personalized cancer immunotherapy. These neoantigens arise from somatic mutations, such as single nucleotide variants or frameshifts, that are unique to an individual's tumor and absent in healthy tissue (Nature Reviews Cancer, 2021). In the context of dendritic cells, these mutated proteins are captured, processed, and displayed on MHC Class I and Class II molecules to initiate a robust immune response (Frontiers in Immunology, 2020). This presentation is essential for the priming of naive T cells, enabling them to recognize and eliminate tumor cells that display the same neoepitopes (Science, 2017). Therapeutic interventions targeting these complexes include personalized mRNA vaccines, peptide vaccines, and adoptive T-cell therapies (Cell, 2019). Because these targets are truly tumor-specific, they offer the potential for high therapeutic efficacy with minimal off-target toxicity compared to conventional shared-antigen therapies (Journal of Hematology & Oncology, 2019).

Other names
Tumor-specific neoantigensNeoepitopesPersonalized tumor antigensMHC-restricted neoantigensTumor-specific antigens (TSA)
02

Mechanism of action

Induction of tumor-specific T-cell responses through the delivery of patient-specific mutated sequences that are processed and presented by dendritic cells to prime and activate cytotoxic CD8+ and helper CD4+ T lymphocytes (Science, 2017).

03

Biological functions

Immune responseAntigen presentationT-cell activationImmune surveillance
04

Disease associations

CancerSolid tumorMelanomaNon-small cell lung cancer
05

Safety considerations

Immune-related adverse events (irAEs)Potential for cross-reactivity with self-antigensManufacturing complexity and time-to-treatmentAntigen loss or tumor heterogeneityInjection site reactions
06

Interacting drugs

mRNA-4157 (V940)

4 more in the full profile.

07

Biomarkers

Tumor Mutational Burden (TMB)HLA-typingNeoantigen loadT-cell receptor (TCR) repertoireMicrosatellite instability (MSI) status

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