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

项目总结 Vaxiion建议评估细菌微细胞作为免疫调节疗法用于 中高危非肌肉浸润性膀胱癌(NMIBC)。建议的产品将是 配方和标签用于膀胱内给药，并由细菌微细胞组成，经工程设计 具有增强的抗肿瘤和免疫调节特性。Vaxiion已经初步证明 微细胞可以被设计成在静脉注射时具有增强的抗肿瘤活性 不同的人类癌症临床前模型，现在试图探索将微细胞用作 免疫调节疗法用于中高危NMIBC患者，目前的标准是 护理是膀胱镜下经尿道膀胱肿瘤电切术(TURBT)，14天后行膀胱内电切术 活细菌卡介苗(BCG)的给药。因为推荐的治疗方法 卡介苗耐药、卡介苗耐药或卡介苗复发的NMIBC患者指南(45-50%)和 对于那些对卡介苗不耐受的患者(~20%)，立即行膀胱切除和尿流改道，这将使患者 以急性和慢性发病率的形式造成的严重损失，我们认为在这一患者群体中存在重大机会。 Vaxiion的微型细胞非常适合这项工作，因为它们缺乏细菌染色体，而且是无生命的 因此，可以提供卡介苗的免疫调节益处，而不存在与生存相关的毒性。减少 在保持免疫调节益处的同时保持毒性将是用于治疗的产品的一个有用的特征 卡介苗失败和卡介苗不耐受患者面临膀胱切除术。此外，微型细胞，与活着形成鲜明对比 卡介苗可能有潜力在TURBT后立即给予。在这里实施辅助治疗 已知在低风险NMIBC患者中，使用化疗药物的时间可以产生更好的结果，但因为 与对照组相比，它们对中危患者的益处较小，对高危患者则没有益处。 卡介苗、化疗药物不常使用。TURBT术后立即开始卡介苗治疗可能是理想的 中高危患者，但不幸的是，TURBT相关膀胱穿孔的风险(S)领先 对致命的系统性卡介苗感染是令人望而却步的。Vaxiion打算使用一个 杜兰大学在W.T.Godbey博士的实验室开发的一套高度专业化的模型，以及 成功后，开始临床前开发一种用于NMIBC的微型细胞产品。

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.