Targeting Neoantigens for Personalised Immunotherapy.
Antonia L PritchardPublished in: BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy (2018)
This review discusses the rapidly evolving field of immunotherapy research, focusing on the types of cancer antigens that can be recognised by the immune system and potential methods by which neoantigens can be exploited clinically to successfully target and clear tumour cells. Recent studies suggest that the likelihood of successful immunotherapeutic targeting of cancer will be reliant on immune response to neoantigens. This type of cancer-specific antigen arises from somatic variants that result in alteration of the expressed protein sequence. Massively parallel sequencing techniques now allow the rapid identification of these genomic mutations, and algorithms can be used to predict those that will be processed by the proteasome, bind to the transporter complex and encode peptides that bind strongly to individual MHC molecules. The emerging data from assessment of the immunogenicity of neoantigens suggests that only a minority of mutations will form targetable epitopes and therefore the potential for immunotherapeutic targeting will be greater in cancers with a higher frequency of protein-altering somatic variants. It is evident that neoantigens contribute to the success of some immunotherapeutic interventions and that there is significant scope for specific targeting of these antigens to develop new treatment approaches.
Keyphrases
- papillary thyroid
- copy number
- squamous cell
- cancer therapy
- machine learning
- childhood cancer
- induced apoptosis
- amino acid
- squamous cell carcinoma
- young adults
- dendritic cells
- lymph node metastasis
- binding protein
- deep learning
- protein protein
- dna methylation
- oxidative stress
- signaling pathway
- immune response
- single cell
- electronic health record
- genome wide
- cell death
- smoking cessation
- big data