Tiptuximab Immunotherapeutic for Cancer

Tiptuximab 癌症免疫疗法

基本信息

批准号：
8830123
负责人：
DENNIS E HALLAHAN
金额：
$ 22.5万
依托单位：
MEDICAL GUIDANCE SYSTEMS, LLC
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-26 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8830123
关键词：
Acidosis Address Agreement Animals Antibodies Antigens Antineoplastic Agents Binding Biodistribution Biotechnology Breast Cancer Center Cancer Patient Cancer Prognosis Clinical Clinical Research Clinical Trials Colon Carcinoma Data Development Disease Drug Delivery Systems Effector Cell Epidermal Growth Factor Receptor Feasibility Studies Funding Glioblastoma Glucose Goals Head and neck structure Heterogeneity Human Hypoglycemia Hypoxia IgG1 Image Immune Immune response Immunotherapeutic agent In Vitro Intellectual Property Intravenous infusion procedures Laboratories Lead Licensing Malignant Neoplasms Malignant neoplasm of lung Malignant neoplasm of pancreas Marketing Medical Monoclonal Antibodies Mus Natural Killer Cells Normal tissue morphology Patients Pharmaceutical Preparations Pharmacologic Substance Phase Pre-Clinical Model Process Proteins Radiation Radiation therapy Radioimmunoconjugate Radiolabeled Radiopharmaceuticals Research Research Proposals Small Business Technology Transfer Research Specificity Stress Surface Survival Rate System Taxes Technology Therapeutic Agents Therapeutic Effect Therapeutic antibodies Universities Washington base biological adaptation to stress cancer cell cancer therapy chemotherapeutic agent commercial application commercialization dosimetry drug development efficacy testing genetic regulatory protein humanized antibody irradiation meetings mouse model novel therapeutics oncology overexpression pre-clinical preclinical efficacy preclinical safety public health relevance radiotracer receptor response safety testing technological innovation

项目摘要

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.

描述（由申请人提供）：肺癌、胶质母细胞瘤、胰腺癌等预后不良的癌症的 3 年生存率在 1%-15% 之间，治疗性抗体开发的最新进展在乳腺癌、头颈癌、癌症等其他癌症中显示出了希望。抗体开发的局限性在于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，我们在放射治疗过程中发现并优先考虑了癌症中的诱导抗原。表现出正常组织中未观察到的过度应激反应，我们在多种癌症中发现了 39 种诱导蛋白，这些蛋白优先考虑了癌症特异性和显示诱导抗原的广泛癌症亚型。显示癌症特异性和在癌细胞表面的长期结合在拟议的 STTR 中，我们将表征tiptuximab，这是一种与癌症上的辐射诱导 TIP1 特异性结合的治疗抗体。通过开发针对不良预后癌症的抗体来满足未满足的医疗需求。更具体地说，肺癌是肿瘤学中最大的市场之一，我们的目标是将抗体纳入临床试验，以证明专门针对癌症的治疗性抗体的概念的临床证明。通过利用诱导性抗原，我们确定了优先顺序。我们基于癌症特异性和功效的领先小鼠单克隆抗体，接下来我们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 2 期 STTR 研究，该研究将为临床前安全性和后续临床提供资金。该抗体的研究目的是：1）对肺癌小鼠模型中的放射性标记抗体进行成像2）研究tiptuximab在人体中激活的免疫反应。这项研究将通过展示癌症诱导抗原抗体的新开发范例来推进癌症药物开发领域。这项研究还将解决开发新的肺癌治疗药物方面未得到满足的医疗需求。