Identification of Neoantigens from lncRNA-Encoded Micropeptides in Kidney Cancer
Abstract
It has become clear now that the human genome can make two types of genes: (1) ones that can produce proteins, i.e., protein-coding genes, and (2) those that lack the ability to produce proteins, i.e., non-coding genes or non-coding RNAs. Both types of genes are important to our body. Recent evidence suggests that although, by definition, non-coding RNAs do not make proteins, a number of non-coding RNAs can indeed generate small peptides, or micropeptides, that are much smaller in size than proteins. More importantly, these micropetides have been shown to play a role in normal cell functions or disease processes. However, the function of the vast majority of such micropeptides is not known. In particular, it is not clear whether they can play any role in kidney cancer. Therefore, this application aims to test a hypothesis of whether long non-coding RNA-encoded micropeptides can serve as neoantigens because such neoantigens would facilitate the development of novel immunotherapy. It is well known that immunotherapy offers a great hope to cancer patients. However, the overall response in kidney cancer is still relatively low largely due to a lack of comprehensive understanding of the details in immunotherapy, including tumor mutational burden, which is critical to generation of neoantigens for immunotherapy. Since neoantigens can be used to develop personalized, cancer-specific vaccines, they could play a critical role in immunotherapy. Common approaches for identification of neoantigens are through sophisticated processes. Thus, the innovative aspect of this application lies in identification of such neoantigens from peptides encoded by long non-coding RNAs and this has never been explored in kidney cancer. The overall objective of this application is to identify candidate neoantigens from long non-coding RNA-encoded micropeptides, and then to evaluate their immunogenicity. Identification of such micropeptides will provide a novel approach to immunotherapy in kidney cancer. As a result, these potential micropetides can ultimately be tested in clinical applications and directly benefit kidney cancer patients. Therefore, this application addresses the FY21 KCRP Focus Area Develop novel therapeutic strategies for the treatment of kidney cancer, such as novel drug targets, therapeutic modalities and agents, treatment combinations and drug delivery systems.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210095
Entities
People
- Xinchun Zhou
Organizations
- United States Army
- University of Mississippi Medical Center