Abstract
According to the latest available data, cancer is the second leading cause of death, highlighting the need for novel cancer therapeutic approaches. In this context, immunotherapy is emerging as a reliable first-line treatment for many cancers, particularly metastatic melanoma. Indeed, cancer immunotherapy has attracted great interest following the recent clinical approval of antibodies targeting immune checkpoint molecules, such as PD-1, PD-L1, and CTLA-4, that release the brakes of the immune system, thus reviving a field otherwise poorly explored. Cancer immunotherapy mainly relies on the generation and stimulation of cytotoxic CD8 T lymphocytes (CTLs) within the tumor microenvironment (TME), priming T cells and establishing efficient and durable anti-tumor immunity. Therefore, there is a clear need to define and identify immunogenic T cell epitopes to use in therapeutic cancer vaccines. Naturally presented antigens in the human leucocyte antigen-1 (HLA-I) complex on the tumor surface are the main protagonists in evocating a specific anti-tumor CD8+ T cell response. However, the methodologies for their identification have been a major bottleneck for their reliable characterization. Consequently, the field of antigen discovery has yet to improve. The current review is intended to define what are today known as tumor antigens, with a main focus on CTL antigenic peptides. We also review the techniques developed and employed to date for antigen discovery, exploring both the direct elution of HLA-I peptides and the in silico prediction of epitopes. Finally, the last part of the review analyses the future challenges and direction of the antigen discovery field.
Highlights
The recent clinical success of antibodies targeting immune checkpoint molecules, such as programmed death receptor-1 (PD-1), its ligand PD-L1, and cytotoxic T cell-associated antigen 4(CTL-A4), have led to a new and strong interest in the field of cancer immunotherapy [1,2]
The sample was applied to a series of columns, each one respectively coupled with the monoclonal antibodies anti-human leucocytes antigen (HLA)-A02, anti-HLA-B07, and anti-pan human leucocyte antigen-1 (HLA-I)
Assuming that longer lasting epitope presentation increases the likelihood of T cell recognition, they show that pMHC stability better correlates with immunogenicity than HLA binding affinity
Summary
The recent clinical success of antibodies targeting immune checkpoint molecules, such as programmed death receptor-1 (PD-1), its ligand PD-L1, and cytotoxic T cell-associated antigen 4. Approaches can benefit from the use of epitope prediction tools to combine two kinds of information: the differential gene expression in cancer compared to matched healthy tissue and the probability of those candidates to be presented on the cell surface onto the HLA molecule [17,18]. NGS and in silico tools are effective methods in antigen discovery; improvements are needed These methods lack rich and experimentally validated datasets, decreasing the accuracy of the predictive algorithms. It describes the concept of antigens, focusing mainly on CTL antigenic peptides It provides a concise analysis of the methods endorsed for the antigen discovery process, including in vitro and in silico approaches.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
