could circular rna provide new immunotherapy targets?

With his Young Investigator Award, Dr. Chen will focus on circular RNAs (circRNAs), a novel class of non-canonical RNA with potential to provide new targets for cancer immunotherapy. By leveraging circRNAs to identify new cancer neoantigens, Dr. Chen aims to develop innovative cancer vaccines and enhance targeted cancer treatment strategies. Cancer neoantigens are special marker proteins that only show up on cancer cells due to mutations in the cancer cell genome. These cancer-specific markers are critical in enabling the body’s immune cells to distinguish between normal cells and cancer cells, allowing immune cells to specifically target and eliminate cancer cells. The identification of novel neoantigens holds immense potential in cancer immunotherapy; traditionally, neoantigens were thought to arise from mutations in the mRNA of cancer cells, leading to the production of these unique marker proteins. However, this concept faces limitations, as many cancer cells exhibit only a few mutations, resulting in the rarity of these markers and leading to significant challenges in identifying effective cancer vaccine targets.

Dr. Chen leveraged his innovative circRNA screening technology with a proteomic analysis workflow to identify the immune-peptomic profile of cancer cells and has discovered that some of circRNA-derived proteins can act as neoantigens because they are exclusive to cancer cells and are not found in healthy cells. This discovery opens a new avenue in for sourcing neoantigen targets from the previously unexplored realm of circRNAs. In this project Dr. Chen will assess the therapeutic efficacy and effects of cancer vaccines targeting circRNA-derived neoantigens, evaluating their impact on cancer cells both in cellular and mouse models. Using innovative tools he has developed to identify RNA protein interaction and to screen circular RNA, cutting edge computer modeling, and a strong group of supporting cancer biologists and cancer immunologists, he hopes to lead the way to developing innovative cancer vaccines and to enhancing targeted cancer treatment strategies.