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

优化革兰氏阳性菌作为靶向抗肿瘤治疗的候选者

基本信息

批准号：
10204711
负责人：
Bentley M. Shuster
金额：
$ 5.7万
依托单位：
COLUMBIA UNIV NEW YORK MORNINGSIDE
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10204711
关键词：
3-Dimensional Aerobic Affective Animal Model Antineoplastic Agents Bacillus Bacillus licheniformis Bacillus megaterium Bacillus subtilis Bacteria Biological Biological Response Modifier Therapy Biomedical Engineering CT26 Cause of Death Cells Coculture Techniques Colon Carcinoma Colorectal Communities Culture Media Dose-Limiting Drug Delivery Systems Engineered Gene Engineering Escherichia coli Exposure to Genes Genetic Genetic Engineering Genome Gram-Negative Bacteria Gram-Positive Bacteria Growth In Vitro Knock-out Laboratories Lead Libraries Malignant Neoplasms Mediating Medical Research Membrane Methods Microscopy Modeling Modernization Mole the mammal Natto Oncologist Organism Pathway interactions Patients Peptide Hydrolases Peptide Signal Sequences Plasmid Cloning Vector Plasmids Probiotics Production Proteins Publishing Rapid screening Recombinant Proteins Reporter Research Research Proposals Safety Salmonella typhimurium Scientist Site Testing Therapeutic Therapeutic Uses Time Toxic effect Toxin Treatment Protocols anti-cancer antimicrobial cancer cell cancer therapy cytotoxic efficacy testing experimental study follow-up high throughput screening immunogenicity in vivo in vivo optical imaging innovation microbial colonization mouse model multimodality mutant novel programs protein expression quorum sensing routine Bacterial stain synthetic biology targeted cancer therapy time use tool tumor tumor growth tumor hypoxia tumor microenvironment

项目摘要

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.

项目总结/摘要癌症是全球第二大死亡原因，许多可用的治疗方法缺乏安全性和有效性，肿瘤学家和病人都在寻找的答案。已经做出了重大努力来利用活生物体，例如细菌，作为产生和递送位点特异性治疗有效载荷的载体，然而它们大多是cen，针对革兰氏阴性细菌进行试验。在这项建议中，我们的目标是扩大候选人名单，可供probi- 通过探索芽孢杆菌属物种在肿瘤微环境中定植的潜力来治疗耳癌。许多芽孢杆菌属物种通常被认为是安全的（GRAS），并且由于革兰氏阳性菌能够高亲合性，蛋白产物分泌。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，以开发抗癌疗法的革兰氏阳性生产中心。使用细菌- 球体共培养（BSCC）模型，我们可以快速筛选最佳的分离物和重组蛋白产品并使用体内小鼠模型进行仅探索高预成形候选品系的后续实验。通过体外和体内方法，我们的目标是开发新的，安全的，有效的替代治疗肿瘤生长和提高癌症治疗的质量。