An innovative in situ cell reprogramming technology for cancer treatment

描述（由申请人提供）：我们发明了一种创新的蛋白质诱导多能干细胞（piPSCs）技术，该技术可以在1周内从正常成纤维细胞和癌细胞中生成piPSCs，转化效率为90% - 4%。如此高的转换效率使我们能够在患癌动物的癌症中开创原位细胞重编程技术。我们不是在培养皿中生成iPSCs，而是在体内进行细胞重编程，将癌细胞转化为piPSCs，使其立即分化为组织内的非癌细胞，从而使癌变组织能够被正常细胞修复。使用皮下肿瘤大鼠模型，我们证明了这种基于蛋白质诱导的多能性原位细胞重编程提供了一种有效的细胞转化疗法，通过将恶性胶质瘤细胞原位转化为iPSCs分化为非癌性胶质瘤，从而治愈皮下胶质瘤

DESCRIPTION (provided by applicant): We invented an innovative protein induced Pluripotent Stem Cells (piPSCs) technology that generates piPSCs from normal fibroblast and cancer cells within 1-week with 90¿4% conversion efficiency. Such high conversion efficiency enables us to pioneer an in situ cell reprogramming technology within the cancers of cancer-bearing animals. Instead of generating iPSCs in a dish, we perform cell reprogramming in vivo to convert cancer cells into piPSCs that immediately differentiate into non-cancerous cells inside tissues, allowing cancerous tissues to be repaired by normal cells. Using a subcutaneous cancer rat model, we demonstrated that this protein-induced pluripotency- based in situ cell reprogramming provided an effective cell-converting therapy to cure subcutaneous glioma via the in situ conversion of malignant glioma cells into iPSCs for differentiation into non- cancerous cells under the differentiation tissue environment. We applied our QQ-protein delivery technique and daily intra-tumor injections to deliver Sox2, Oct4 and Nanog (SON) proteins directly into the cancer cells to initiate and execute this novel cancer cell conversion. In this proposal, we will optimize this in situ cell reprogramming technology using the same cancer rat model. Two injection methods will be performed to treat subcutaneous glioma-bearing rats: intra- tumor (Aim 1) and intravenous injections (Aim 2). Our goal is to achieve nearly 100% subcutaneous glioma cured rats to provide proof-of-principle data of high efficacy of diseased tissue repair using this technology. In order to achieve this goal, we will optimize the SON protein dosages, injection frequency and period and different QQ-modifications to treat early and late state subcutaneous implanted gliomas. We will also collect safety data of this treatment by measuring tissue distributions and possible pathological changes in the organs caused by the injected SON proteins. Although subcutaneously implanted glioma rat model is not a physiological animal model for human glioma, this model provides a convenient and effective cancer animal model for us to optimize this innovative technology which is the central focus of this Phase I STTR proposal. The success of this proposal will allow us to develop a paradigm-shifting cell reprogramming technology to treat many diseases using the Nobel-winning iPSC concept. This will also provide QURGEN Inc. with many commercialization possibilities. The success of this proposal will further position us to pursue glioma treatment using physiologically relevant intracranial implanted human glioma nude rat models.