In situ vaccination of lung cancers with engineered dendritic cells combined with immunotherapy
Abstracts
Initial Award Abstract |
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Lung cancer is the most common cause of cancer death worldwide with approximately 85% of patients having non-small cell lung cancer (NSCLC). Tobacco smoking plays a major role in the development of lung cancer, accounting for more than 80% of cases in the United States. The current treatment landscape for NSCLC has evolved with the use of drugs that enhance the immune system's ability to destroy cancer cells. However, only approximately 20% of patients with progressive, locally advanced or metastatic NSCLC show a robust and durable response to such immunotherapy. One mechanism lung cancers develop resistance to immunotherapy involves the loss of the activity of a gene called Lkb1, which leads to an immunosuppressive environment. We propose to develop a treatment approach that involves injecting immune cells (dendritic cells) directly into the tumor. These cells will be gene-modified to overproduce two proteins, CXCL9 and CXCL10, which are important signaling molecules that orchestrate the immune system's anti-tumor activity. Thus, we hypothesize that this approach can potentiate the response to standard immunotherapy by enhancing the ability of the immune system to recognize the tumor and to promote tumor-specific immune cell activation. This treatment paradigm targets the immunosuppressive properties of Lkb1-deficient tumors, which can potentially demonstrate improved personalized treatment that takes advantage of the genetic markers of a patient's tumor. Therapies tailored to individual cancer patients can potentially lead to better prognosis. |
