Target intelligence / Profile preview

Tumor neoantigen peptide–Major Histocompatibility Complex (NeoAg-MHC) (NeoAg-MHC)

Target
NeoAg-MHC
Molecular classification
Other (Antigen-MHC complex), Protein complex, Receptor-ligand complex
01

Overview

Tumor neoantigen peptide–Major Histocompatibility Complex (MHC) complexes are unique molecular signatures presented on the surface of malignant cells, resulting from somatic mutations that create novel, non-self peptides (Nature Reviews Cancer, 2019). These peptides are processed and presented by MHC molecules, allowing the immune system to distinguish cancer cells from healthy tissue (NIH NCI). Because neoantigens are absent from the normal proteome, they represent highly specific targets for immunotherapy, minimizing the risk of central tolerance and autoimmunity (Science, 2017). Therapeutic strategies targeting these complexes include personalized vaccines, TCR-engineered T-cells, and antibody-like molecules that recognize specific peptide-HLA combinations (Frontiers in Immunology, 2020). The efficacy of these treatments often depends on the patient's HLA genotype and the stability of the peptide-MHC interaction (Journal of Hematology & Oncology, 2021). These targets are central to the development of precision immuno-oncology, where treatments are tailored to the unique genetic landscape of an individual's tumor.

Other names
Neoepitope-MHC complexTumor-specific antigen-MHC complexpHMCNeoantigen-HLA complexTSA-MHC complex
02

Mechanism of action

Induction of neoantigen-specific T-cell responses via active immunization (vaccines); direct targeting of peptide-MHC complexes by engineered T-cell receptors (TCR-T) or bispecific antibodies to induce tumor cell lysis.

03

Biological functions

Antigen presentationImmune responseT-cell activationImmune surveillance
04

Disease associations

CancerSolid tumorHematological malignancy
05

Safety considerations

Off-target toxicity due to molecular mimicry with self-peptidesImmune escape through HLA downregulation or loss of heterozygosity (LOH)Cytokine release syndrome (CRS)Antigenic driftLow frequency of high-affinity neoantigens
06

Interacting drugs

mRNA-4157 (V940)

6 more in the full profile.

07

Biomarkers

Tumor Mutational Burden (TMB)HLA-A/B/C typingNeoantigen loadMicrosatellite instability (MSI)T-cell receptor (TCR) repertoire diversity

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