Development of Personalized Therapeutic Cancer Vaccines to Effectively Mobilize Antitumor T-Cell Immunity in Non-Small Cell Lung Cancer
Abstract
The immune system can specifically eradicate tumor cells, yet the potential to harness this ability in the treatment of cancer has been, at best, limited. Treatment fails because a strong anti-tumor immune response is not elicited in most patients, highlighting the need to devise better ways to activate the host T cells against the tumor. Unfortunately, because tumors are complex and made up of individualized types of cancer cells, training the immune system to recognize these different cells has been difficult. This means that current therapies leave behind many of the cancer cells that are unique to any given patient and fail to completely eliminate the disease, allowing the tumor to grow back. In this proposal, our overarching goal is to address these gaps in cancer immunotherapy so that the majority of patients benefit from improved quality of life and extended survival. To elicit coordinated and robust anti-tumor immune responses, we are developing a novel class of personalized cell therapies via generation of tumor-reactive T cells from patients with non-small cell lung cancer (NSCLC). NSCLC represents a significant national health burden as the leading cause of cancer-related deaths in the United States, impacting the health and well-being of the American public and disproportionally affecting United States military Service Members. By using an innovative priming method, we will harness each patient’s unique biology to direct immune recognition and elimination of the diverse cells comprising their tumor. We will employ an advanced preclinical model to assess the sensitivity of tumor cells to T cell mediated attack at the individual patient level. Ultimately, we seek to improve patient outcomes and overcome treatment resistance in NSCLC by addressing two areas of emphasis: (1) identify innovative strategies for the treatment of lung cancer, and (2) understand mechanisms of resistance to treatment. An improved understanding of the mechanisms limiting therapeutic response will derive from gene expression analyses of the tumor at the single cell level throughout treatment. Importantly, the methods and preclinical platform described herein can readily be adapted to other tumor types, broadening the clinical applicability of the proposed technologies. As such, this research represents a potentially game changing step toward personalized cancer treatment.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110393
Entities
People
- Stephanie Hachey
Organizations
- United States Army
- University of California, Irvine