Targeting ART1, a Novel Immune Checkpoint, for the Treatment of Lung Cancer

We propose to study the role of a protein called ART1 in lung cancer. ART1 has not been previously described in lung tumors, but we have found several clues to suggest that it might play a role in lung cancer progression. In our proposal, we plan to test a therapeutic antibody that blocks the actions of ART1. We anticipate that this antibody will decrease tumor growth and metastasis by blocking the ability of ART1 to kill T cells. Such treatment strategies have already shown great success in lung cancer by using antibody-based drugs that block checkpoint inhibitors such as PD1 or PD-L1. In our application, we propose to 1) test anti-ART1 antibodies against lung cancer in mouse models with normal immune systems, 2) test combination therapy of anti-ART1 antibodies with immune therapy and radiation therapy, and 3) evaluate ART1 expression and its relationship to immune cells, particularly T cells expressing P2X7R, in a variety of human lung tumors and try to understand the role of ART1 expression in patients treated with radiation therapy or immunotherapy. We anticipate that an anti-ART1 therapeutic antibody will have a tremendous impact on lung cancer patients, offering another type of immunotherapy which helps to release the brakes on T cells and unleash the patients own immune system on his or her cancer.