Poor prognosis cancers such as lung cancer, glioblastoma, pancreatic cancer and others have 3 year survival rates that range from 1%-15%. Recent advancements in the development of therapeutic antibodies have shown promise in other cancers such as breast, head and neck, and colon cancer. The limitations in antibody development are the paucity of cancer specific antigens and the heterogeneity within cancer cells. To address these limitations, we have discovered and prioritized inducible antigens in cancer. During treatment with radiation, cancer demonstrates an exaggerated stress response that is not observed in normal tissues. We have discovered 39 inducible proteins in a wide range of cancers. These have been prioritized upon cancer specificity and the wide spectrum of cancer subtypes that show induction. Our lead antibody to inducible antigen shows cancer specificity and prolonged binding on the surface of cancer cells. In the proposed STTR, we will characterize tiptuximab, which is a therapeutic antibody that binds specifically to radiation inducible TIP1 on cancer. This research proposal addresses an unmet medical need through the development of antibodies to poor prognosis cancers. More specifically, lung cancer is among the largest markets in oncology. Our goal is to bring the antibody into clinical trials to demonstrate the clinical proof of concept of targeting therapeutic antibodies specifically to cancer by exploiting inducible antigens. We have prioritized our lead mouse monoclonal antibody based on cancer specificity and efficacy. We next humanized this antibody and will now conduct preclinical imaging and biodistribution studies. Following the preclinical proof of concept, we will apply for Phase 2 STTR studies which will fund preclinical safety and subsequent clinical studies of the antibody. The goals of the proposed research are to: 1) Image the radiolabeled antibody in mouse models of lung cancer. 2) Study the immune response activated by tiptuximab in human cancers. This research will advance the field of cancer drug development by demonstrating a new paradigm of development of antibodies to inducible antigens in cancer. This research will also address an unmet medical need in developing new therapeutic agents to lung cancer.