Optimizing Gram-positive bacteria as a candidate for targeted anti-tumor therapy

项目摘要/摘要 癌症是全球第二大死亡原因，许多现有的治疗方法缺乏安全性和有效性. 肿瘤学家和患者都在寻求环磷酰胺。已经做出了重大努力来利用活的生物体，例如 细菌作为产生和传递特定部位治疗有效载荷的载体，然而它们大多集中在- 以革兰氏阴性细菌为基础。在这项建议中，我们的目标是扩大可供提名的候选人名单- 通过探索芽孢杆菌物种在肿瘤微环境中定植的潜力来进行耳科癌症治疗。 许多芽孢杆菌通常被认为是安全的(GRAS)，而作为革兰氏阳性菌能够对 乳头产物分泌物。因此，我们还将致力于扩展模式生物芽孢杆菌的遗传工具箱 枯草杆菌，以开发抗癌治疗的革兰氏阳性生产中心。使用细菌在- 球体共培养(BSCC)模型，我们可以快速筛选出最佳的分离株和重组蛋白产品 并使用活体小鼠模型进行后续实验，仅探索高预成型候选菌株。 通过体外和体内方法，我们的目标是开发出治疗肿瘤的新的、安全的和有效的替代品。 增长和提高癌症治疗的质量。

PROJECT SUMMARY/ABSTRACT Cancer is the second leading cause of death globally and many available treatments lack the safety and effica- cy sought by oncologists and patients alike. Major efforts have been made to use living organisms, such as bacteria, as vehicles to produce and deliver site-specific therapeutic payloads, however they are mostly cen- tered on Gram-negative bacteria. In this proposal, we aim to expand the list of candidates available for probi- otic cancer therapy by exploring the potential for species of Bacillus to colonize tumor microenvironments. Many Bacillus species are generally regarded as safe (GRAS) and as Gram-positives are capable of high pro- tein product secretion. Therefore, we will also aim to expand the genetic toolbox for model organism, Bacillus subtilis, in order to develop Gram-positive production hubs of anticancer therapies. Using the bacteria-in- spheroid coculture (BSCC) model, we can rapidly screen for optimal isolates and recombinant protein products and use in vivo mouse models for follow up experiments exploring only the high preforming candidate strains. With in vitro and in vivo approaches, we aim to develop novel, safe, and effective alternatives to treat tumor growth and increase the quality of cancer therapy.