Engineering a new versican remodeling recombinant bacterial product to enable immunotherapy success in triple negative breast cancer

设计一种新的多功能蛋白重塑重组细菌产品，使三阴性乳腺癌免疫治疗取得成功

• 批准号: 10027945
• 金额: $ 50.46万
• 依托单位: NEOBE THERAPEUTICS LTD
• 依托单位国家: 英国
• 项目类别: Collaborative R&D
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=10027945
• 关键词: Engineering; new; versican; remodeling; recombinant

The cancer therapeutics field has been revolutionized by immunotherapy. The development of drugs that recruit the immune system to recognize and eliminate cancer cells has led to an extraordinary increase in patient survival, in some tumour types. However, only around 20% of patients with solid tumours are estimated to currently benefit from them. Multiple factors contribute to this low level of efficacy. Chief among them is the existence of biophysical barriers that prevent the infiltration of immune cells in a subset of patients. Previous studies have shown that removing these barriers can increase immune infiltration. However, this approach has not worked in the clinic, due to either insufficient penetration of the tumour core by these drugs leading to poor efficacy, or toxicities associated with systemic drug delivery.Neobe Therapeutics is a start up developing innovative live biotherapeutic products to disrupt these barriers from within. By acting locally within the tumour, these products will effectively increase immune infiltration while avoiding associated toxicities. Our products are designed to be delivered systemically and engineered to colonize the tumour core, respond to its local environment and remodel it from within, circumventing previous constraints. In this project we will develop a new bacterial product targeting a specific component of the tumour microenvironment associated with decreased immune infiltration in patients with triple negative breast cancer. The product is being designed based on data from the laboratory of Dr. Oliver Pearce at Queen Mary University of London, a collaborator on this project. We will engineer multiple prototypes and select the most effective one using state of the art cancer models. Our prototype will be a lead asset of a new class of live therapeutic products that alter the local environment of solid tumours from within, leading to the generation of a platform for future drug development upon project completion. More importantly, successful development and eventual commercialization of this project could expand the benefits of immunotherapies to thousands of patients with triple negative breast cancer.The project is led by Neobe Therapeutics, founded by scientists with years of experience in this field, in both academic and industry settings. Neobe was spun out from a collaboration between Cancer Research UK and Deep Science Ventures, who will continue to be associated with this project to ensure its success. Our collaboration with Queen Mary will provide the necessary expertise on barriers to immune infiltration to guarantee product efficacy.

癌症治疗领域已经被免疫疗法彻底改变。招募免疫系统来识别和消除癌细胞的药物的开发已经导致某些肿瘤类型的患者生存率显著提高。然而，据估计，目前只有约20%的实体瘤患者从中受益。多种因素导致这种低水平的功效。其中最主要的是生物物理屏障的存在，阻止了免疫细胞在一部分患者中的浸润。以前的研究表明，去除这些屏障可以增加免疫浸润。然而，这种方法在临床上并不奏效，因为这些药物对肿瘤核心的渗透不足导致疗效不佳，或者与全身给药相关的毒性。Neobe Therapeutics是一家开发创新的活生物素产品的初创公司，旨在从内部破坏这些屏障。通过在肿瘤内局部作用，这些产品将有效地增加免疫浸润，同时避免相关毒性。我们的产品旨在系统性地提供，并经过工程设计，以殖民肿瘤核心，对其局部环境做出反应，并从内部对其进行改造，从而绕过以前的限制。在这个项目中，我们将开发一种新的细菌产品，靶向与三阴性乳腺癌患者免疫浸润减少相关的肿瘤微环境的特定成分。该产品是根据伦敦玛丽女王大学奥利弗皮尔斯博士实验室的数据设计的，他是该项目的合作者。我们将设计多个原型，并使用最先进的癌症模型选择最有效的一个。我们的原型将成为一类新的活体治疗产品的主要资产，这些产品从内部改变实体瘤的局部环境，从而在项目完成后为未来的药物开发提供平台。更重要的是，该项目的成功开发和最终商业化可以将免疫疗法的益处扩大到数千名三阴性乳腺癌患者。该项目由Neobe Therapeutics领导，由在该领域拥有多年经验的科学家创立，在学术和行业环境中。Neobe是英国癌症研究中心和Deep Science Ventures合作的产物，Deep Science Ventures将继续参与该项目，以确保其成功。我们与玛丽女王的合作将提供必要的专业知识，对免疫渗透的障碍，以保证产品的疗效。