SBIR Topic 255: Evaluate Therapeutic Potential of Novel Immunomodulator, Imprime

SBIR 主题 255：评估新型免疫调节剂 Imprime 的治疗潜力

• 批准号: 8164227
• 负责人: MARY ANTONYSAMY
• 金额: $ 15.91万
• 依托单位: BIOTHERA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-30 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8164227
• 关键词: SBIR; Topic; 255; Evaluate; Therapeutic

Pancreatic cancer is a "rare" and fata l disease, with few treatment options. Currently, promising antitumor strategies utilize combination therapies, with each agent targeting separate aspects of oncogenesis. Disappointingly, combination of anti- EGFR monoclonal antibody (MAb), cetuximab, with standard-of-care, gemcitabine, failed to improve survival in this disease. Although EGFR is over-expressed in >90% of pancreatic carcinomas -90% also contain KRAS mutations. We herein propose a strategy that could overcome resistance of KRAS mutations to anti-EGFR MAbs. Biothera is developing Imprime-PGG¿, a beta 1,3/1,6 glucose polymer, as an adjunct to MAbs for cancer treatment. The proprietary agent, Imprime, induces neutrophil-mediated cellular cytotoxicity, where Imprime 'primes' neutrophils (comprise -50%-70% of human immune cells) to recognize and kill MAb targeted tumors. Preclinically, Imprime has shown therapeutic efficacy as an adjunct to MAbs in various tumor models, including KRAS-mutated lung and colon carcinoma models. This coupled wi th the safety and recent efficacy data from a Phase 1 b/2 metastatic CRC study supports Imprime to be a safe and effective drug. Overall objective is to establish preclinical proof of concept for this novel treatment approach in pancreatic cancer xenografts; both KRAS-wild type and KRASmutant tumors will be studied, and subsequently evaluate therapeutic potential in the clinic.

胰腺癌是一种“罕见”和致命的疾病，几乎没有治疗选择。目前，有前途的抗肿瘤策略利用联合疗法，每种药物靶向肿瘤发生的不同方面。令人遗憾的是，抗EGFR单克隆抗体（MAb）西妥昔单抗与标准治疗吉西他滨的组合未能改善这种疾病的存活率。虽然EGFR在>90%的胰腺癌中过表达，但90%也含有KRAS突变。我们在此提出了一种可以克服KRAS突变对抗EGFR单克隆抗体的耐药性的策略。Biothera正在开发Imprime-PGG，一种β 1，3/1，6葡萄糖聚合物，作为MAbs治疗癌症的辅助药物。专有试剂Imprime诱导嗜中性粒细胞介导的细胞毒性，其中Imprime“引发”嗜中性粒细胞（包含约50%-70%的人免疫细胞）识别并杀死MAb靶向的肿瘤。在临床前，Imprime已在各种肿瘤模型（包括KRAS突变的肺癌和结肠癌模型）中显示出作为MAb辅助治疗的疗效。这与I期B/II期转移性CRC研究的安全性和近期疗效数据相结合，支持Imprime是一种安全有效的药物。总体目标是为胰腺癌异种移植物中的这种新型治疗方法建立临床前概念证明;将研究KRAS野生型和KRAS突变型肿瘤，并随后评估临床治疗潜力。