Determinants for Neoantigen Identification

Abstract

All tumors accumulate genetic alterations, some of which can give rise to mutated, non-self peptides presented by human leukocyte antigen (HLA) molecules and elicit T-cell responses. These immunogenic mutated peptides, or neoantigens, are foreign in nature and display exquisite tumor specificity. The correlative evidence suggesting they play an important role in the effectiveness of various cancer immunotherapies has triggered the development of vaccines and adoptive T-cell therapies targeting them. However, the systematic identification of personalized neoantigens in cancer patients, a critical requisite for the success of these therapies, remains challenging. A growing amount of evidence supports that only a small fraction of all tumor somatic non-synonymous mutations (NSM) identified represent bona fide neoantigens; mutated peptides that are processed, presented on the cell surface HLA molecules of cancer cells and are capable of triggering immune responses in patients. Here, we provide an overview of the existing strategies to identify candidate neoantigens and to evaluate their immunogenicity, two factors that impact on neoantigen identification. We will focus on their strengths and limitations to allow readers to rationally select and apply the most suitable method for their specific laboratory setting.

Adoptive Cell Therapy Targeting Neoantigens: A Frontier for Cancer Research

“…The combination of WES and MS has become a powerful weapon for exploring neoantigens in tumor immune therapy. Andrea Garcia-Garijo further applied this method to make a difference in mining neoantigens in melanoma and renal cell carcinoma, and gave detailed illustrations of the identification of tumor-specific non-synonymous mutations and the evaluation of immunogenicity of candidate neoantigens (34).…”

Insights Into Lung Cancer Immune-Based Biology, Prevention, and Treatment

“…A special category of these antigens comprises neoantigens, which are present on MHC molecules (38,39) (Figure 1). Surprisingly, neoantigens are unique to the patient rather than to the tumor, and are often downregulated in tumors, suggesting that tumors evade immune destruction (40)(41)(42)(43)(44)(45). These properties make neoantigens suitable targets for personalizing cancer vaccines and ACT (46,47).…”

Mass Spectrometry-Based Identification of MHC-Associated Peptides

“…Until recently, most efforts in neoantigen identification were performed with indirect methods, relying on genome and transcriptome sequences [18,46,47]. This information can be used to detect mutations and confirm the transcription of the variant DNA sequences.…”