Utilizing immunogenomic approaches to prioritize targetable neoantigens for personalized cancer immunotherapy. Front Immunol 2023;14:1301100
Date
12/27/2023Pubmed ID
38149253Pubmed Central ID
PMC10749952DOI
10.3389/fimmu.2023.1301100Scopus ID
2-s2.0-85180411127 (requires institutional sign-in at Scopus site)Abstract
Advancements in sequencing technologies and bioinformatics algorithms have expanded our ability to identify tumor-specific somatic mutation-derived antigens (neoantigens). While recent studies have shown neoantigens to be compelling targets for cancer immunotherapy due to their foreign nature and high immunogenicity, the need for increasingly accurate and cost-effective approaches to rapidly identify neoantigens remains a challenging task, but essential for successful cancer immunotherapy. Currently, gene expression analysis and algorithms for variant calling can be used to generate lists of mutational profiles across patients, but more care is needed to curate these lists and prioritize the candidate neoantigens most capable of inducing an immune response. A growing amount of evidence suggests that only a handful of somatic mutations predicted by mutational profiling approaches act as immunogenic neoantigens. Hence, unbiased screening of all candidate neoantigens predicted by Whole Genome Sequencing/Whole Exome Sequencing may be necessary to more comprehensively access the full spectrum of immunogenic neoepitopes. Once putative cancer neoantigens are identified, one of the largest bottlenecks in translating these neoantigens into actionable targets for cell-based therapies is identifying the cognate T cell receptors (TCRs) capable of recognizing these neoantigens. While many TCR-directed screening and validation assays have utilized bulk samples in the past, there has been a recent surge in the number of single-cell assays that provide a more granular understanding of the factors governing TCR-pMHC interactions. The goal of this review is to provide an overview of existing strategies to identify candidate neoantigens using genomics-based approaches and methods for assessing neoantigen immunogenicity. Additionally, applications, prospects, and limitations of some of the current single-cell technologies will be discussed. Finally, we will briefly summarize some of the recent models that have been used to predict TCR antigen specificity and analyze the TCR receptor repertoire.
Author List
Shah RK, Cygan E, Kozlik T, Colina A, Zamora AEAuthor
Anthony E. Zamora PhD Assistant Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Antigens, NeoplasmHumans
Immunotherapy
Mutation
Neoplasms
Receptors, Antigen, T-Cell
