Tiptuximab Immunotherapeutic for Cancer

 描述(由申请人提供)： 预后不良的癌症，如肺癌、胶质母细胞瘤、胰腺癌等，3年生存率在1%-15%之间。治疗性抗体的最新进展显示出在其他癌症如乳腺癌、头颈部和结肠癌中的应用前景。抗体开发的局限性是癌症特异性抗原的缺乏和癌细胞内的异质性。为了解决这些局限性，我们发现了癌症中的诱导抗原，并将其列为优先考虑的因素。在放射治疗期间，癌症表现出正常组织中没有观察到的夸大的应激反应。我们已经在多种癌症中发现了39种可诱导蛋白。这些都是根据癌症的特异性和显示诱导性的癌症亚型的广谱而优先考虑的。我们的抗诱导性抗原的铅抗体显示了癌症的特异性和对癌细胞表面的长时间结合。在建议的STTR中，我们将描述替普昔单抗的特征，它是一种治疗性抗体，专门与癌症上的辐射诱导TIP1结合。这项研究建议通过开发针对预后不良的癌症的抗体来解决未得到满足的医学需求。更具体地说，肺癌是肿瘤学最大的市场之一。我们的目标是将该抗体带入临床试验，以证明通过利用可诱导的抗原来靶向针对癌症的治疗性抗体的概念的临床证据。我们已经优先考虑 我们的主导鼠单抗基于肿瘤的特异性和有效性。我们接下来将这种抗体人源化，现在将进行临床前成像和生物分布研究。在临床前概念验证之后，我们将申请第二阶段STTR研究，这将为抗体的临床前安全性和随后的临床研究提供资金。本研究的目的是：1)在小鼠肺癌模型中对放射性标记抗体进行成像。2)研究替普昔单抗在人类肿瘤中激活的免疫反应。这项研究将通过展示一种新的癌症诱导抗原抗体开发范式来推动癌症药物开发领域的发展。这项研究还将解决在开发新的肺癌治疗剂方面尚未得到满足的医学需求。

 DESCRIPTION (provided by applicant): 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.