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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）：预后不良的癌症，如肺癌、胶质母细胞瘤、胰腺癌等，3年生存率为1%-15%。治疗性抗体开发的最新进展已显示出在其他癌症如乳腺癌、头颈癌和结肠癌中的前景。抗体开发的限制是缺乏癌症特异性抗原和癌细胞内的异质性。为了解决这些局限性，我们已经发现并优先考虑了癌症中的诱导抗原。在放射治疗期间，癌症表现出在正常组织中未观察到的过度应激反应。我们已经在多种癌症中发现了39种诱导蛋白。这些优先考虑癌症特异性和广泛的癌症亚型，显示诱导。我们的诱导型抗原的先导抗体显示出癌症特异性和在癌细胞表面的延长结合。在拟议的STTR中，我们将描述tiptuximab，这是一种治疗性抗体，可特异性结合癌症上的辐射诱导型TIP 1。这项研究提案通过开发预后不良癌症的抗体来解决未满足的医疗需求。更具体地说，肺癌是肿瘤学最大的市场之一。我们的目标是将抗体带入临床试验，以证明通过利用诱导抗原特异性靶向癌症的治疗性抗体的临床概念证明。我们优先考虑我们领先的小鼠单克隆抗体基于癌症特异性和功效。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2期STTR研究，该研究将资助抗体的临床前安全性和后续临床研究。本研究的目的是：1）在小鼠肺癌模型中对放射性标记的抗体进行成像。2)研究人类癌症中由tipuximab激活的免疫应答。这项研究将通过展示开发针对癌症中诱导抗原的抗体的新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的未满足的医疗需求。