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

免疫疗法使癌症治疗领域发生了革命性的变化。利用免疫系统识别和消灭癌细胞的药物的发展，极大地提高了某些肿瘤患者的存活率。然而，据估计，目前只有约20%的实体瘤患者从中受益。多种因素导致了这种低水平的疗效。其中最主要的是存在生物物理屏障，防止免疫细胞在一部分患者中浸润。先前的研究表明，清除这些屏障可以增加免疫渗透。然而，由于这些药物对肿瘤核心的渗透不足导致疗效不佳，或者与全身药物递送相关的毒性，这种方法在临床中尚未奏效。Neobe Therapeutics是一家开发创新活生物治疗产品的初创公司，旨在从内部打破这些障碍。通过局部作用于肿瘤，这些产品将有效地增加免疫浸润，同时避免相关的毒性。我们的产品被设计成系统地输送，并被设计成在肿瘤核心定植，对其局部环境做出反应，并从内部对其进行改造，绕过之前的限制。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。该产品是根据该项目的合作者、伦敦玛丽皇后大学奥利弗·皮尔斯博士实验室的数据设计的。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，这些产品可以从内部改变实体肿瘤的局部环境，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展到成千上万的三阴性乳腺癌患者。该项目由Neobe Therapeutics公司领导，该公司由在该领域具有多年学术和行业经验的科学家创立。Neobe是从英国癌症研究中心和深度科学风险投资公司的合作中分离出来的，后者将继续参与该项目，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，以防止免疫渗透，以保证产品的功效。

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.