Target intelligence / Profile preview

Patient-specific tumor neoantigen peptides bound to Major Histocompatibility Complex (MHC) (Neoantigen-MHC complex)

Target
Neoantigen-MHC complex
Molecular classification
Antigen-MHC complex, Protein-peptide complex, Receptor-ligand complex
01

Overview

Patient-specific tumor neoantigen peptides bound to Major Histocompatibility Complex (MHC) represent a class of highly specific targets for personalized cancer immunotherapy. These neoantigens arise from somatic mutations—such as single nucleotide variants, insertions, or deletions—within the tumor genome that result in novel, non-self protein sequences (Schumacher & Schreiber, 2015, Science). When these mutated proteins are processed and presented by MHC molecules on the tumor cell surface, they can be recognized by the host's T-cell receptors as foreign (Sahin et al., 2017, Nature). Because neoantigens are absent from healthy tissues, they offer a high degree of therapeutic selectivity and a lower risk of central tolerance compared to traditional tumor-associated antigens (Blass & Ott, 2021, Nature Reviews Clinical Oncology). Current therapeutic approaches include personalized vaccines (mRNA, DNA, or peptide-based) and adoptive cell therapies using T-cells engineered with neoantigen-specific receptors (Ott et al., 2017, Nature). These interventions are designed to stimulate a robust, targeted cytotoxic immune response against the malignancy while sparing normal cells (Hu et al., 2021, Nature Reviews Immunology).

Other names
Tumor-specific antigens (TSAs)NeoepitopesNeoantigen-HLA complexesPersonalized cancer antigensMutanome-derived epitopes
02

Mechanism of action

Induction of de novo T-cell responses or expansion of existing neoantigen-specific T-cells to recognize and lyse tumor cells presenting the specific peptide-MHC complex.

03

Biological functions

Antigen presentationT-cell activationImmune responseImmune surveillance
04

Disease associations

CancerSolid tumorsMelanomaNon-small cell lung cancerColorectal cancer
05

Safety considerations

Off-target toxicity due to cross-reactivity with wild-type proteinsCytokine release syndrome (CRS)Immune-related adverse events (irAEs)Antigen escape or lossHLA downregulation by tumor cells
06

Interacting drugs

mRNA-4157 (V940)

4 more in the full profile.

07

Biomarkers

Tumor Mutational Burden (TMB)HLA typingNeoantigen loadT-cell receptor (TCR) repertoire sequencingMicrosatellite instability (MSI)

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