哥伦比亚大学Tal Danino研究团队近日取得一项新成果，他们揭示了可编程细菌可诱导持久性肿瘤消退和全身性抗肿瘤免疫。这一研究成果于2019年7月发表在国际顶尖学术期刊《自然—医学》上。

研究人员设计了一株非致病性大肠杆菌菌株，能够特异性地在肿瘤微环境中裂解并释放编码的CD47纳米抗体拮抗剂 (CD47nb)， CD47是一种抗吞噬细胞吞噬的受体，通常在几种人类癌症细胞中过表达。研究发现，在同基因型小鼠肿瘤模型中，肿瘤定植菌传递CD47nb可以增加肿瘤浸润T细胞的活化，刺激肿瘤快速消退，防止转移，使得肿瘤小鼠长期存活。此外，课题组还报道了局部注射CD47nb表达细菌可刺激全身性肿瘤抗原特异性免疫反应，从而降低未治疗肿瘤的生长，为工程细菌免疫治疗引发远端效应这一概念研究提供了有效证明。因此，工程菌可实现安全的局部免疫治疗载体输送，进而实现全身性抗肿瘤免疫。

研究人员表示，合成生物学通过活细胞基因编程，正在推动医学进入一个新的时代。这种革命性的方法能够创建对不同环境产生智能感知和响应的工程系统。该系统能够增加治疗的特异性和有效性，超出了常规分子疗法的能力。其中一个独特的研究领域是将细菌作为治疗传递系统，在体内选择性释放治疗载体。

附：英文原文

Title: Programmable bacteria induce durable tumor regression and systemic antitumor immunity

Author: Sreyan Chowdhury, Samuel Castro, Courtney Coker, Taylor E. Hinchliffe, Nicholas Arpaia, Tal Danino

Issue&Volume: Volume 25 Issue 7, July 2019

Abstract: Synthetic biology is driving a new era of medicine through the genetic programming of living cells. This transformative approach allows for the creation of engineered systems that intelligently sense and respond to diverse environments, ultimately adding specificity and efficacy that extends beyond the capabilities of molecular-based therapeutics. One particular area of focus has been the engineering of bacteria as therapeutic delivery systems to selectively release therapeutic payloads in vivo.Here we engineered a non-pathogenic Escherichia coli strain to specifically lyse within the tumor microenvironment and release an encoded nanobody antagonist of CD47 (CD47nb), an anti-phagocytic receptor that is commonly overexpressed in several human cancer types. We show that delivery of CD47nb by tumor-colonizing bacteria increases activation of tumor-infiltrating T cells, stimulates rapid tumor regression, prevents metastasis and leads to long-term survival in a syngeneic tumor model in mice. Moreover, we report that local injection of CD47nb-expressing bacteria stimulates systemic tumor-antigen-specific immune responses that reduce the growth of untreated tumors, providing proof-of-concept for an abscopal effect induced by an engineered bacterial immunotherapy. Thus, engineered bacteria may be used for safe and local delivery of immunotherapeutic payloads leading to systemic antitumor immunity.

DOI: 10.1038/s41591-019-0498-z

Source: https://www.nature.com/articles/s41591-019-0498-z