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原文传递 EMT Targeting Vaccination, Concurrent with Chemoimmunotherapy, in Advanced NSCLC.

题名：	EMT Targeting Vaccination, Concurrent with Chemoimmunotherapy, in Advanced NSCLC.
作者：	Riolobos, L.
摘要：	Immunotherapy is a significant treatment advance for non-small cell lung cancer (NSCLC) and the only therapy thatcan lead to long term survival, although this occurs in less than 20% of patients. Patients receiving chemo-immunotherapy vs chemotherapy alone demonstrated a significantly longer survival. Despite this improvement, themajority of patients die within 2 years of diagnosis. High levels of tumor infiltrating lymphocytes (TIL) predictresponse to immune checkpoint inhibitor (ICI) therapy in animal models and lung cancer patients. Unfortunately,high levels of TIL are found in less than 10% 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 clinicaloutcomes. Strategies, such as vaccines, to increase CD8+ TIL could synergize ICI and improve survival in allNSCLC patients with advanced disease. Vaccines are able to induce tumor specific immunity and increase CD8 TILin animal models.Using novel techniques, we have developed STEMVAC, a multi-antigen vaccine targeting proteins in the epithelialto mesenchymal transition (EMT) pathway. EMT is the process by which anchorage dependent cancer cells developthe capacity to metastasize. We have identified upregulated proteins on the EMT pathway that are immunogenic andhave defined in these proteins Type I CD4+ Th1 selective epitopes. CD4 Th1 immunity supports the generation ofCD8+ cytotoxic T-cells. In animal models, STEMVAC profoundly inhibits cancer growth and results in theelimination 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.
总页数：	11 pages