Cytokine Gene Transfer for Metastatic Colorectal Cancer

描述(由申请人提供)： 转移性结肠癌在美国是一个重大的医疗问题，每年有5万新诊断病例，中位生存期不到2年。结肠癌肿瘤相关抗原的鉴定为评价免疫治疗策略提供了依据。尽管在一些癌症中显示出希望，但由于应答率低和毒性高，使用系统细胞因子注射的免疫治疗在很大程度上令人失望。肿瘤内基因转移已被提出作为一种替代给药手段，以改善这些分子的治疗和毒理学特征。不幸的是，由于缺乏临床可行的基因传递载体，临床应用受到阻碍。最近对体内电穿孔的研究表明，在肿瘤内给药方面有了显著的改善。Ichor开发了专有的电穿孔技术，使该程序能够安全有效地应用。初步的临床前工作表明，Ichor系统是一种很有前途的肿瘤内细胞因子基因输送方法。在FLAIR阶段-L下，Ichor将评估其将细胞因子基因输送到肝结肠癌转移瘤的电穿孔技术。研究将包括旨在建立有效治疗方案的啮齿动物研究。成功的完成将导致在FLAIR阶段LI下对无法切除的结直肠转移患者进行正式的毒理学研究和随后的临床研究。

DESCRIPTION (provided by applicant): Metastatic colon cancer represents a significant healthcare problem in the U.S., with 50,000 new cases diagnosed annually and median survival at less than 2 years. The identification of tumor-associated antigens in colon cancer provides the basis to evaluate immunological treatment strategies. Despite showing promise in some cancers, immunotherapy using systemic cytokine administration has largely disappointed due to low response rates and high toxicity. Intratumoral gene transfer has been proposed as an alternative means of administration to improve the therapeutic and toxicologic profile of these molecules. Unfortunately, clinical implementation is hampered by the lack of clinically viable gene delivery vectors. Recent studies of in vivo electroporation demonstrate dramatic improvement in intratumoral delivery of therapeutic agents. Ichor has developed proprietary electroporation technology enabling safe and effective application of the procedure. Initial preclinical work suggests that Ichor's system is a promising means for intratumoral cytokine gene delivery. Under FLAIR Phase-l, Ichor will evaluate its electroporation technology for delivery of cytokine genes into hepatic colon cancer metastases. Research will include rodent studies designed to establish effective treatment protocols. Successful completion will lead to formal toxicology studies and subsequent clinical investigation of the procedure in patients with unresectable colorectal metastases, conducted under FLAIR Phase-lI.