Development of a novel class of immunotherapeutic antibody for metastatic prostate cancer

开发一类新型治疗转移性前列腺癌的免疫治疗抗体

基本信息

批准号：
10017200
负责人：
GRANT H RISDON
金额：
$ 68.1万
依托单位：
CANCURE, LLC
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-12 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10017200
关键词：
Address Androgen Receptor Antibodies Antigen-Antibody Complex Antigens Benchmarking Biochemical Biophysics CD3 Antigens CD34 gene CD8-Positive T-Lymphocytes Cancer Center Cancer Patient Cell surface Clinical Clinical Trials Collaborations Colon Consult Data Development Development Plans Fostering Future Goals Human Immune Immunosuppression Immunotherapeutic agent Immunotherapy Impairment Licensing Ligands Mediating Metastatic Neoplasm to the Bone Metastatic Prostate Cancer Modeling Monoclonal Antibodies Myeloid-derived suppressor cells Natural Killer Cells Neoplasm Metastasis Outcome Patients Pharmaceutical Preparations Phase I Clinical Trials Pre-Clinical Model Production Prostate Recommendation Risk Safety Serum Signaling Molecule Solid Neoplasm Stress Surface Technology Testing Toxic effect Toxicology Translating Treatment Efficacy base checkpoint therapy clinical development clinical toxicology commercialization drug development early phase clinical trial first-in-human human monoclonal antibodies immune checkpoint blockade improved interest macrophage meetings mouse model mutant nonhuman primate novel novel therapeutics pre-clinical preclinical development preclinical study preclinical toxicity prostate cancer cell receptor safety testing self-renewal targeted treatment tumor

项目摘要

Abstract The overarching goal of this application is to development a novel immunotherapy for treatment of metastatic prostate cancer (mPC), a lethal with limited treatment options. Immunotherapy has significantly improved survival in patients with a variety of solid tumors, however it has only presented limited efficacy in metastatic prostate cancer patients. Thus, there is an unmet need to develop effective immunotherapies for mPC. Based on the findings that metastatic prostate tumor cells convert the stress-induced immune stimulatory cell surface molecule, the MHC I Chain related molecule (MIC), to a highly immune suppressive soluble MIC (sMIC). CanCure has developed a first-in-class sMIC-targeting monoclonal antibody (mAb) B10G5 that has demonstrated remarkable efficacy in eliminating prostate metastatic as a single agent in preclinical models. When used in combination, B10G5 synergizes with immune checkpoint blockade therapy and eliminates immune checkpoint therapy-induced colon toxicity. We show that B10G5 confers its therapeutic efficacy through two defined mechanisms of action. CanCure has formulated the B10G5 mAb for human use (designated and huB10G5) and tested the safety of huB10G5 in pilot toxicity study in non-human primates (NHP). HuB10G5 is ready for IND-enabling studies. To achieve our goal, CanCure proposes two specific Aims: 1) Determine therapeutic efficacy of B10G5 with frontline AR-targeting therapy for mPC; 2) Conduct pre-clinical IND-enabling GLP production and toxicology study. The outcome of proposed study would define the path and provide a strong scientific rationale on how to translate our new therapy into early clinical trials. .

抽象的该申请的总体目标是开发一种新型免疫疗法来治疗转移性癌症前列腺癌（mPC）是一种致命的癌症，治疗选择有限。免疫疗法显着提高生存率在患有多种实体瘤的患者中，但它对转移性前列腺的疗效有限癌症患者。因此，开发针对 mPC 的有效免疫疗法的需求尚未得到满足。基于研究结果表明，转移性前列腺肿瘤细胞会转化应激诱导的免疫刺激细胞表面分子，MHC I 链相关分子 (MIC) 到高度免疫抑制可溶性 MIC (sMIC)。 CanCure 开发了一流的 sMIC 靶向单克隆抗体 (mAb) B10G5，该抗体具有在临床前模型中显示出作为单一药物消除前列腺转移的显着功效。当联合使用时，B10G5 与免疫检查点阻断疗法具有协同作用，并消除免疫检查点治疗引起的结肠毒性。我们通过两种方式证明 B10G5 具有治疗功效明确的行动机制。 CanCure 已配制出供人类使用的 B10G5 mAb（指定和 huB10G5），并在非人类灵长类动物（NHP）的初步毒性研究中测试了 huB10G5 的安全性。 HuB10G5 是为 IND 支持研究做好准备。为了实现我们的目标，CanCure 提出了两个具体目标：1) 确定 B10G5与一线AR靶向治疗对mPC的治疗效果； 2) 进行临床前 IND 启用 GLP生产和毒理学研究。拟议研究的结果将确定路径并提供强有力的支持关于如何将我们的新疗法转化为早期临床试验的科学原理。。