EMT Targeting Vaccination, Concurrent with Chemoimmunotherapy, in Advanced NSCLC
Abstract
Immunotherapy is a significant treatment advance for non-small cell lung cancer (NSCLC) and the only therapy that can lead to long term survival, although this occurs in less than 20 percent of patients. Patients receiving chemoimmunotherapy vs chemotherapy alone demonstrated a significantly longer survival. Despite this improvement, the majority of patients die within 2 years of diagnosis. High levels of tumor infiltrating lymphocytes (TIL) predict response to immune checkpoint inhibitor (ICI) therapy in animal models and lung cancer patients. Unfortunately, high levels of TIL are found in less than 10 percent of patients and a quarter of NSCLC patients have no evidence of TIL. Presence of CD8+ TIL is an independent prognostic variable in NSCLC and is associated with improved clinical outcomes. Strategies, such as vaccines, to increase CD8+ TIL could synergize ICI and improve survival in all NSCLC patients with advanced disease. Vaccines are able to induce tumor specific immunity and increase CD8 TIL in animal models. Using novel techniques, we have developed STEMVAC, a multi-antigen vaccine targeting proteins in the epithelial to mesenchymal transition (EMT) pathway. EMT is the process by which anchorage dependent cancer cells develop the capacity to metastasize. We have identified upregulated proteins on the EMT pathway that are immunogenic and have defined in these proteins Type I CD4+ Th1 selective epitopes. CD4 Th1 immunity supports the generation of CD8+ cytotoxic T-cells. In animal models, STEMVAC profoundly inhibits cancer growth and results in the elimination of cells expressing EMT proteins. A Phase I trial has shown STEMVAC to be safe and immunogenic, generating high levels of peripheral blood antigen specific T-cells; similar to the levels reported with mutation based vaccines suggesting Th1 selective epitopes act as neo-antigens.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2023
- Accession Number
- AD1205237
Entities
People
- Rafael Santana-davila
Organizations
- University of Washington