Immunotherapeutic minicells for use in intermediate and high-risk non-muscle inva

项目摘要 Vaxiion建议评估细菌小细胞作为免疫调节治疗的潜力， 中度和高风险非肌肉浸润性膀胱癌（NMIBC）。拟议的产品将是 配制并标记用于膀胱内给药，并且由细菌小细胞组成，经工程改造以 具有增强的抗肿瘤和免疫调节特性。Vaxiion已经初步证明， 可以将小细胞工程化以当在几个实施方案中静脉内施用时具有增强的抗肿瘤活性。 不同的人类癌症临床前模型，现在寻求探索使用微细胞作为治疗癌症的可能性。 免疫调节治疗用于中等和高风险NMIBC患者，其中目前的标准 护理是膀胱肿瘤的细胞镜经尿道电切术（TURBT），14天后进行膀胱内 施用活细菌卡介苗（BCG）。因为推荐的治疗方法 BCG难治性、BCG耐药或BCG复发（共45 - 50%）的NMIBC患者指南， 对于那些BCG不耐受的患者（约20%），立即进行膀胱灌注和尿流改道， 急性和慢性疾病的形式造成了严重的损失，我们认为在这一患者群体中存在着重大的机会。 Vaxiion的微细胞非常适合这项工作，因为它们缺乏细菌染色体并且是非生命的， 因此可以提供BCG的免疫调节益处而没有活力相关的毒性。减少 毒性同时保持免疫调节益处将是用于治疗的产品的有用特征 BCG失败和BCG不耐受患者面临化疗。此外，微细胞，与活细胞形成鲜明对比， BCG可能在TURBT后立即给予。此时给予辅助治疗 已知在低风险NMIBC患者中使用化疗药物会产生更好的结果，但由于 在中危患者中获益较少，在高危患者中无获益， BCG、化疗药物不常使用。在TURBT后立即开始卡介苗治疗可能是理想的， 中度和高风险患者，但不幸的是，TURBT相关膀胱穿孔的风险导致 致命的全身性BCG感染是禁止的。Vaxiion打算使用一个 在杜兰大学的W.T.博士的实验室中开发的一套高度专业化的模型。戈德比，以及 成功后，开始临床前开发用于NMIBC的微细胞产品。

PROJECT SUMMARY Vaxiion proposes to evaluate the potential for bacterial minicells as an immunomodulatory therapy for use in intermediate and high-risk non-muscle invasive bladder cancer (NMIBC). The proposed product would be formulated and labeled for intravesical administration and be comprised of bacterial minicells, engineered to have enhanced anti-tumor and immunomodulatory properties. Vaxiion has preliminarily demonstrated that minicells can be engineered to have enhanced anti-tumor activity when administered intravenously in several different pre-clinical models of human cancer and now seeks to explore the possibility of using minicells as an immunomodulatory therapy for use in intermediate and high-risk NMIBC patients where the current standard of care is cytoscopic transuretheral resection of bladder tumor (TURBT) followed 14 days later by the intravesical administration of a live bacterium, Bacillus Calmette-Guerin (BCG). Because the recommended treatment guideline for NMIBC patients that are BCG-refractory, BCG-resistant, or BCG-relapsed (together 45-50%) and for those patients that are BCG-intolerant (~20%) is immediate cystectomy and urinary diversion, which exacts a heavy toll in the form of acute and chronic morbidity, we feel major opportunity in this patient population exist. Vaxiion's minicells are well suited for the job because they lack bacterial chromosomes and are non-living, and therefore may provide the immunomodulatory benefits of BCG without viability-associated toxicity. Reducing toxicity while maintaining immunomodulatory benefit would be a useful characteristic of a product used to treat BCG failure and BCG intolerant patients who face cystectomy. Additionally, minicells, in stark contrast to live BCG, may have the potential to be given immediately post-TURBT. Administration of adjuvant therapy at this time is known to produce better outcomes using chemotherapeutics in low-risk NMIBC patients but because they provide less benefit in intermediate-risk patients and no benefit in high-risk patients when compared to BCG, chemotherapeutics are not often used. It may be ideal to start BCG therapy immediately post-TURBT in intermediate and high-risk patients, but, unfortunately, the risk of TURBT-related bladder perforation(s) leading to fatal systemic BCG infection is prohibitive. Vaxiion intends to test the feasibility of this approach using a highly specialized set of models developed at Tulane University in the laboratory of Dr. W.T. Godbey, and when successful, begin pre-clinical development of a minicell product for use in NMIBC.