Targeting eEF-2 Kinase to Overcome Therapeutic Resistance in Lung Cancer
Abstract
By determining the role and importance of the eukaryotic elongation factor-2 kinase (eEF-2K) in regulation of T cells and tumor cells and in modulation of immune response, this application wishes to design and develop novel and more effective strategy for improving immunotherapy for patients with lung cancer. Recent development of novel immunotherapy has led to impressive advances in treatment of various types of cancer, including lung cancer. Immunotherapy, such as adoptive cell transfer-based therapy (ACT), is now a viable option for patients with this notorious disease; yet clinical outcome of ACT is limited by various pathophysiological factors, and key molecular players in regulation of therapeutic immunity remain elusive. Of note, recent studies have revealed that the metabolic status of both immune cells and tumor cells can have a great impact on antitumor immunity. eEF-2K is a highly unusual protein kinase that regulates protein synthesis; is greatly expressed in most immune cells and various types of malignancy; and is critically required for survival of stressed cells. Moreover, recent studies strongly suggest that this unique protein kinase is critically involved in determining antitumor immunity, implying that eEF-2K might be exploited as a novel therapeutic target for modulating immune response and that inhibitors of this kinase may have the potential to be utilized as effective immunomodulators for lung cancer therapy. The overall goal of this project is to understand the precise role of eEF-2K in tumor immune evasion and define this kinase as a novel immunomodulatory target. The long-term innovation of this project is developing eEF-2K-targeted immunomodulatory strategies for significantly improving treatment for lung cancer. ACT has shown extraordinary promise in treatment of cancers. Nevertheless, tumor cells may display a remarkable capacity to resist the onslaught of immune-therapeutic modalities, and this largely limits the success and benefits of immunotherapy. eEF-2K may have pivotal roles in regulating antitumor immunity. This project will focus on defining the precise roles and mechanisms of eEF-2K in controlling T cells and in regulating immune-tumor microenvironment (TME). Success of this project will not only reveal eEF-2K as a novel immunomodulatory target involved in tumor immune evasion and yield new knowledge about the pathological roles of eEF-2K, but also uncover new therapeutic opportunities to improve lung cancer immunotherapy through eEF-2K-targeted strategy. Collectively, identifying novel molecular targets and the mechanisms involved in tumor immune evasion may facilitate development of new strategies to improving tumor responsiveness to lung cancer immunotherapy.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210053
Entities
People
- Jianxun Song
Organizations
- Texas A&M Health Science Center
- United States Army